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Targeting the LSD1/KDM1 Family of Lysine Demethylases in Cancer and Other Human Diseases

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Targeting Lysine Demethylases in Cancer and Other Human Diseases

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1433))

Abstract

Lysine-specific demethylase 1 (LSD1) was the first histone demethylase discovered and the founding member of the flavin-dependent lysine demethylase family (KDM1). The human KDM1 family includes KDM1A and KDM1B, which primarily catalyze demethylation of histone H3K4me1/2. The KDM1 family is involved in epigenetic gene regulation and plays important roles in various biological and disease pathogenesis processes, including cell differentiation, embryonic development, hormone signaling, and carcinogenesis. Malfunction of many epigenetic regulators results in complex human diseases, including cancers. Regulators such as KDM1 have become potential therapeutic targets because of the reversibility of epigenetic control of genome function. Indeed, several classes of KDM1-selective small molecule inhibitors have been developed, some of which are currently in clinical trials to treat various cancers. In this chapter, we review the discovery, biochemical, and molecular mechanisms, atomic structure, genetics, biology, and pathology of the KDM1 family of lysine demethylases. Focusing on cancer, we also provide a comprehensive summary of recently developed KDM1 inhibitors and related preclinical and clinical studies to provide a better understanding of the mechanisms of action and applications of these KDM1-specific inhibitors in therapeutic treatment.

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References

  • Abdulla A, Zhao X, Yang F (2013) Natural polyphenols inhibit lysine-specific demethylase-1 in vitro. J Biochem Pharmacol Res 1:56–63

    PubMed  PubMed Central  Google Scholar 

  • Abu-Farha M, Lanouette S, Elisma F, Tremblay V, Butson J, Figeys D, Couture JF (2011) Proteomic analyses of the SMYD family interactomes identify HSP90 as a novel target for SMYD2. J Mol Cell Biol 3:301–308

    Article  CAS  PubMed  Google Scholar 

  • Adamo A, Sese B, Boue S, Castano J, Paramonov I, Barrero MJ, Izpisua Belmonte JC (2011) LSD1 regulates the balance between self-renewal and differentiation in human embryonic stem cells. Nat Cell Biol 13:652–659

    Article  CAS  PubMed  Google Scholar 

  • Anand R, Marmorstein R (2007) Structure and mechanism of lysine-specific demethylase enzymes. J Biol Chem 282:35425–35429

    Article  CAS  PubMed  Google Scholar 

  • Ballas N, Grunseich C, Lu DD, Speh JC, Mandel G (2005) REST and its corepressors mediate plasticity of neuronal gene chromatin throughout neurogenesis. Cell 121:645–657

    Article  CAS  PubMed  Google Scholar 

  • Banck MS, Li S, Nishio H, Wang C, Beutler AS, Walsh MJ (2009) The ZNF217 oncogene is a candidate organizer of repressive histone modifiers. Epigenetics 4:100–106

    Article  CAS  PubMed  Google Scholar 

  • Bannister AJ, Schneider R, Kouzarides T (2002) Histone methylation: dynamic or static? Cell 109:801–806

    Article  CAS  PubMed  Google Scholar 

  • Baron R, Binda C, Tortorici M, McCammon JA, Mattevi A (2011) Molecular mimicry and ligand recognition in binding and catalysis by the histone demethylase LSD1-CoREST complex. Structure 19:212–220

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Baron R, Vellore NA (2012) LSD1/CoREST reversible opening-closing dynamics: discovery of a nanoscale clamp for chromatin and protein binding. Biochemistry 51:3151–3153

    Article  CAS  PubMed  Google Scholar 

  • Basta J, Rauchman M (2015) The nucleosome remodeling and deacetylase complex in development and disease. Transl Res J Labor Clin Med 165:36–47

    CAS  Google Scholar 

  • Baylin SB (2011) Resistance, epigenetics and the cancer ecosystem. Nat Med 17:288–289

    Article  CAS  PubMed  Google Scholar 

  • Baylin SB, Jones PA (2011) A decade of exploring the cancer epigenome—biological and translational implications. Nat Rev Cancer 11:726–734

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Benelkebir H, Hodgkinson C, Duriez PJ, Hayden AL, Bulleid RA, Crabb SJ, Packham G, Ganesan A (2011) Enantioselective synthesis of tranylcypromine analogues as lysine demethylase (LSD1) inhibitors. Bioorg Med Chem 19:3709–3716

    Article  CAS  PubMed  Google Scholar 

  • Bennani-Baiti (2012) Integration of ERα-PELP1-HER2 signaling by LSD1 (KDM1A_AOF2) offers combinatorial therapeutic opportunities to circumventing hormone resistance in breast cancer.pdf. Bennani-Baiti Breast Cancer Res 14:112

    Google Scholar 

  • Benner C, Konovalov S, Mackintosh C, Hutt KR, Stunnenberg R, Garcia-Bassets I (2013) Decoding a signature-based model of transcription cofactor recruitment dictated by cardinal cis-regulatory elements in proximal promoter regions. PLoS Genet 9:e1003906

    Article  PubMed  PubMed Central  Google Scholar 

  • Bennesch MA, Segala G, Wider D, Picard D (2016) LSD1 engages a corepressor complex for the activation of the estrogen receptor alpha by estrogen and cAMP. Nucleic Acids Res 44:8655–8670

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Binda C, Valente S, Romanenghi M, Pilotto S, Cirilli R, Karytinos A, Ciossani G, Botrugno OA, Forneris F, Tardugno M, Edmondson DE, Minucci S, Mattevi A, Mai A (2010) Biochemical, structural, and biological evaluation of tranylcypromine derivatives as inhibitors of histone demethylases LSD1 and LSD2. J Am Chem Soc 132:6827–6833

    Article  CAS  PubMed  Google Scholar 

  • Buckingham M (1994) Molecular biology of muscle development. Cell 78:15–21

    Article  CAS  PubMed  Google Scholar 

  • Burg JM, Link JE, Morgan BS, Heller FJ, Hargrove AE, McCafferty DG (2015) KDM1 class flavin-dependent protein lysine demethylases. Biopolymers 104:213–246

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Castex J, Willmann D, Kanouni T, Arrigoni L, Li Y, Friedrich M, Schleicher M, Wohrle S, Pearson M, Kraut N, Meret M, Manke T, Metzger E, Schule R, Gunther T (2017) Inactivation of Lsd1 triggers senescence in trophoblast stem cells by induction of Sirt4. Cell Death Dis 8:e2631

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chan JK, Sun L, Yang XJ, Zhu G, Wu Z (2003) Functional characterization of an amino-terminal region of HDAC4 that possesses MEF2 binding and transcriptional repressive activity. J Biol Chem 278:23515–23521

    Article  CAS  PubMed  Google Scholar 

  • Chen F, Yang H, Dong Z, Fang J, Wang P, Zhu T, Gong W, Fang R, Shi YG, Li Z, Xu Y (2013) Structural insight into substrate recognition by histone demethylase LSD2/KDM1b. Cell Res 23:306–309

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen L, Vasilatos SN, Qin Y, Katz TA, Cao C, Wu H, Tasdemir N, Levine KM, Oesterreich S, Davidson NE, Huang Y (2017) Functional characterization of lysine-specific demethylase 2 (LSD2/KDM1B) in breast cancer progression. Oncotarget 8:81737–81753

    Article  PubMed  PubMed Central  Google Scholar 

  • Chen L, Xu Y, Xu B, Deng H, Zheng X, Wu C, Jiang J (2014) Over-expression of lysine-specific demethylase 1 predicts tumor progression and poor prognosis in human esophageal cancer. Int J Clin Exp Pathol 7:8929–8934

    PubMed  PubMed Central  Google Scholar 

  • Chen Y, Jie W, Yan W, Zhou K, Xiao Y (2012) Lysine-specific histone demethylase 1 (LSD1): a potential molecular target for tumor therapy. Crit Rev Eukaryot Gene Expr 22:53–59

    Article  CAS  PubMed  Google Scholar 

  • Chen Y, Kim J, Zhang R, Yang X, Zhang Y, Fang J, Chen Z, Teng L, Chen X, Ge H, Atadja P, Li E, Chen T, Qi W (2016) Histone demethylase LSD1 promotes adipocyte differentiation through repressing Wnt signaling. Cell Chem Biol 23:1228–1240

    Article  CAS  PubMed  Google Scholar 

  • Chendrimada TP, Gregory RI, Kumaraswamy E, Norman J, Cooch N, Nishikura K, Shiekhattar R (2005) TRBP recruits the dicer complex to Ago2 for microRNA processing and gene silencing. Nature 436:740–744

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chiappinelli KB, Strissel PL, Desrichard A, Li H, Henke C, Akman B, Hein A, Rote NS, Cope LM, Snyder A, Makarov V, Budhu S, Slamon DJ, Wolchok JD, Pardoll DM, Beckmann MW, Zahnow CA, Merghoub T, Chan TA, Baylin SB, Strick R (2015) Inhibiting DNA methylation causes an interferon response in cancer via dsRNA including endogenous retroviruses. Cell 162:974–986

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chinnadurai G (2007) Transcriptional regulation by C-terminal binding proteins. Int J Biochem Cell Biol 39:1593–1607

    Article  CAS  PubMed  Google Scholar 

  • Cho HS, Suzuki T, Dohmae N, Hayami S, Unoki M, Yoshimatsu M, Toyokawa G, Takawa M, Chen T, Kurash JK, Field HI, Ponder BA, Nakamura Y, Hamamoto R (2011) Demethylation of RB regulator MYPT1 by histone demethylase LSD1 promotes cell cycle progression in cancer cells. Can Res 71:655–660

    Article  CAS  Google Scholar 

  • Choi J, Jang H, Kim H, Kim ST, Cho EJ, Youn HD (2010) Histone demethylase LSD1 is required to induce skeletal muscle differentiation by regulating myogenic factors. Biochem Biophys Res Commun 401:327–332

    Article  CAS  PubMed  Google Scholar 

  • Choi J, Jang H, Kim H, Lee JH, Kim ST, Cho EJ, Youn HD (2014) Modulation of lysine methylation in myocyte enhancer factor 2 during skeletal muscle cell differentiation. Nucleic Acids Res 42:224–234

    Article  CAS  PubMed  Google Scholar 

  • Cimmino L, Dolgalev I, Wang Y, Yoshimi A, Martin GH, Wang J, Ng V, Xia B, Witkowski MT, Mitchell-Flack M, Grillo I, Bakogianni S, Ndiaye-Lobry D, Martin MT, Guillamot M, Banh RS, Xu M, Figueroa ME, Dickins RA, Abdel-Wahab O, Park CY, Tsirigos A, Neel BG, Aifantis I (2017) Restoration of TET2 function blocks aberrant self-renewal and leukemia progression. Cell 170(1079–1095):e1020

    Google Scholar 

  • Cortez V, Mann M, Tekmal S, Suzuki T, Miyata N, Rodriguez-Aguayo C, Lopez-Berestein G, Sood AK, Vadlamudi RK (2012) Targeting the PELP1-KDM1 axis as a potential therapeutic strategy for breast cancer. Breast Cancer Res BCR 14:R108

    Article  CAS  PubMed  Google Scholar 

  • Culhane ea (2006) A mechanism-based inactivator for histone demethylase LSD1.pdf. JACS 128:4536–4537

    Google Scholar 

  • Culhane JC, Szewczuk LM, Liu X, Da G, Marmorstein R, Cole PA (2006) A mechanism-based inactivator for histone demethylase LSD1. J Am Chem Soc 128:4536–4537

    Article  CAS  PubMed  Google Scholar 

  • Culhane JC, Wang D, Yen PM, Cole PA (2010) Comparative analysis of small molecules and histone substrate analogues as LSD1 lysine demethylase inhibitors. J Am Chem Soc 132:3164–3176

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dai XJ, Liu Y, Xiong XP, Xue LP, Zheng YC, Liu HM (2020) Tranylcypromine based lysine-specific demethylase 1 inhibitor: summary and perspective. J Med Chem 63:14197–14215

    Article  CAS  PubMed  Google Scholar 

  • Daniels SM, Melendez-Pena CE, Scarborough RJ, Daher A, Christensen HS, El Far M, Purcell DF, Laine S, Gatignol A (2009) Characterization of the TRBP domain required for dicer interaction and function in RNA interference. BMC Mol Biol 10:38

    Article  PubMed  PubMed Central  Google Scholar 

  • Dawson MA, Kouzarides T (2012) Cancer epigenetics: from mechanism to therapy. Cell 150:12–27

    Article  CAS  PubMed  Google Scholar 

  • Dawson MA, Kouzarides T, Huntly BJ (2012) Targeting epigenetic readers in cancer. N Engl J Med 367:647–657

    Article  CAS  PubMed  Google Scholar 

  • Ding J, Zhang ZM, Xia Y, Liao GQ, Pan Y, Liu S, Zhang Y, Yan ZS (2013) LSD1-mediated epigenetic modification contributes to proliferation and metastasis of colon cancer. Br J Cancer 109:994–1003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dressel U, Bailey PJ, Wang SC, Downes M, Evans RM, Muscat GE (2001) A dynamic role for HDAC7 in MEF2-mediated muscle differentiation. J Biol Chem 276:17007–17013

    Article  CAS  PubMed  Google Scholar 

  • Duan YC, Guan YY, Zhai XY, Ding LN, Qin WP, Shen DD, Liu XQ, Sun XD, Zheng YC, Liu HM (2017) Discovery of resveratrol derivatives as novel LSD1 inhibitors: design, synthesis and their biological evaluation. Eur J Med Chem 126:246–258

    Article  CAS  PubMed  Google Scholar 

  • Duteil D, Metzger E, Willmann D, Karagianni P, Friedrichs N, Greschik H, Gunther T, Buettner R, Talianidis I, Metzger D, Schule R (2014) LSD1 promotes oxidative metabolism of white adipose tissue. Nat Commun 5:4093

    Article  CAS  PubMed  Google Scholar 

  • Duteil D, Tosic M, Willmann D, Georgiadi A, Kanouni T, Schule R (2017) Lsd1 prevents age-programed loss of beige adipocytes. Proc Natl Acad Sci USA 114:5265–5270

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ernst T, Chase AJ, Score J, Hidalgo-Curtis CE, Bryant C, Jones AV, Waghorn K, Zoi K, Ross FM, Reiter A, Hochhaus A, Drexler HG, Duncombe A, Cervantes F, Oscier D, Boultwood J, Grand FH, Cross NC (2010) Inactivating mutations of the histone methyltransferase gene EZH2 in myeloid disorders. Nat Genet 42:722–726

    Article  CAS  PubMed  Google Scholar 

  • Ernst T, Pflug A, Rinke J, Ernst J, Bierbach U, Beck JF, Hochhaus A, Gruhn B (2012) A somatic EZH2 mutation in childhood acute myeloid leukemia. Leukemia 26:1701–1703

    Article  CAS  PubMed  Google Scholar 

  • Etani T, Suzuki T, Naiki T, Naiki-Ito A, Ando R, Iida K, Kawai N, Tozawa K, Miyata N, Kohri K, Takahashi S (2015) NCL1, a highly selective lysine-specific demethylase 1 inhibitor, suppresses prostate cancer without adverse effect. Oncotarget 6:2865–2878

    Article  PubMed  Google Scholar 

  • Fang R, Barbera AJ, Xu Y, Rutenberg M, Leonor T, Bi Q, Lan F, Mei P, Yuan GC, Lian C, Peng J, Cheng D, Sui G, Kaiser UB, Shi Y, Shi YG (2010) Human LSD2/KDM1b/AOF1 regulates gene transcription by modulating intragenic H3K4me2 methylation. Mol Cell 39:222–233

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fang R, Chen F, Dong Z, Hu D, Barbera AJ, Clark EA, Fang J, Yang Y, Mei P, Rutenberg M, Li Z, Zhang Y, Xu Y, Yang H, Wang P, Simon MD, Zhou Q, Li J, Marynick MP, Li X, Lu H, Kaiser UB, Kingston RE, Xu Y, Shi YG (2013) LSD2/KDM1B and its cofactor NPAC/GLYR1 endow a structural and molecular model for regulation of H3K4 demethylation. Mol Cell 49:558–570

    Article  CAS  PubMed  Google Scholar 

  • Fang Y, Liao G, Yu B (2019) LSD1/KDM1A inhibitors in clinical trials: advances and prospects. J Hematol Oncol 12:129

    Article  PubMed  PubMed Central  Google Scholar 

  • Ferrari-Amorotti G, Chiodoni C, Shen F, Cattelani S, Soliera AR, Manzotti G, Grisendi G, Dominici M, Rivasi F, Colombo MP, Fatatis A, Calabretta B (2014) Suppression of invasion and metastasis of triple-negative breast cancer lines by pharmacological or genetic inhibition of slug activity. Neoplasia 16:1047–1058

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Figueroa ME, Abdel-Wahab O, Lu C, Ward PS, Patel J, Shih A, Li Y, Bhagwat N, Vasanthakumar A, Fernandez HF, Tallman MS, Sun Z, Wolniak K, Peeters JK, Liu W, Choe SE, Fantin VR, Paietta E, Lowenberg B, Licht JD, Godley LA, Delwel R, Valk PJ, Thompson CB, Levine RL, Melnick A (2010) Leukemic IDH1 and IDH2 mutations result in a hypermethylation phenotype, disrupt TET2 function, and impair hematopoietic differentiation. Cancer Cell 18:553–567

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fiskus W, Sharma S, Shah B, Portier BP, Devaraj SG, Liu K, Iyer SP, Bearss D, Bhalla KN (2014) Highly effective combination of LSD1 (KDM1A) antagonist and pan-histone deacetylase inhibitor against human AML cells. Leukemia 28:2155–2164

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fiszbein A, Kornblihtt AR (2016) Histone methylation, alternative splicing and neuronal differentiation. Neurogenesis (austin) 3:e1204844

    Article  PubMed  Google Scholar 

  • Flavahan WA, Gaskell E, Bernstein BE (2017) Epigenetic plasticity and the hallmarks of cancer. Science 357

    Google Scholar 

  • Forneris F, Battaglioli E, Mattevi A, Binda C (2009) New roles of flavoproteins in molecular cell biology: histone demethylase LSD1 and chromatin. FEBS J 276:4304–4312

    Article  CAS  PubMed  Google Scholar 

  • Foster CT, Dovey OM, Lezina L, Luo JL, Gant TW, Barlev N, Bradley A, Cowley SM (2010) Lysine-specific demethylase 1 regulates the embryonic transcriptome and CoREST stability. Mol Cell Biol 30:4851–4863

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fuentes P, Canovas J, Berndt FA, Noctor SC, Kukuljan M (2012) CoREST/LSD1 control the development of pyramidal cortical neurons. Cereb Cortex 22:1431–1441

    Article  PubMed  Google Scholar 

  • Gooden DM, Schmidt DM, Pollock JA, Kabadi AM, McCafferty DG (2008) Facile synthesis of substituted trans-2-arylcyclopropylamine inhibitors of the human histone demethylase LSD1 and monoamine oxidases A and B. Bioorg Med Chem Lett 18:3047–3051

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Han Y, Wu C, Lv H, Liu N, Deng H (2015) Novel tranylcypromine/hydroxylcinnamic acid hybrids as lysine-specific demethylase 1 inhibitors with potent antitumor activity. Chem Pharm Bull (tokyo) 63:882–889

    Article  CAS  PubMed  Google Scholar 

  • Harris WJ, Huang X, Lynch JT, Spencer GJ, Hitchin JR, Li Y, Ciceri F, Blaser JG, Greystoke BF, Jordan AM, Miller CJ, Ogilvie DJ, Somervaille TC (2012) The histone demethylase KDM1A sustains the oncogenic potential of MLL-AF9 leukemia stem cells. Cancer Cell 21:473–487

    Article  CAS  PubMed  Google Scholar 

  • Hayami S, Kelly JD, Cho HS, Yoshimatsu M, Unoki M, Tsunoda T, Field HI, Neal DE, Yamaue H, Ponder BA, Nakamura Y, Hamamoto R (2011) Overexpression of LSD1 contributes to human carcinogenesis through chromatin regulation in various cancers. Int J Cancer 128:574–586

    Article  CAS  PubMed  Google Scholar 

  • He YF, Li BZ, Li Z, Liu P, Wang Y, Tang Q, Ding J, Jia Y, Chen Z, Li L, Sun Y, Li X, Dai Q, Song CX, Zhang K, He C, Xu GL (2011) Tet-mediated formation of 5-carboxylcytosine and its excision by TDG in mammalian DNA. Science 333:1303–1307

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hino S, Kohrogi K, Nakao M (2016) Histone demethylase LSD1 controls the phenotypic plasticity of cancer cells. Cancer Sci 107:1187–1192

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hino S, Sakamoto A, Nagaoka K, Anan K, Wang Y, Mimasu S, Umehara T, Yokoyama S, Kosai K, Nakao M (2012) FAD-dependent lysine-specific demethylase-1 regulates cellular energy expenditure. Nat Commun 3:758

    Article  PubMed  Google Scholar 

  • Hirano K, Namihira M (2016) LSD1 mediates neuronal differentiation of human fetal neural stem cells by controlling the expression of a novel target gene, HEYL. Stem Cells 34:1872–1882

    Article  CAS  PubMed  Google Scholar 

  • Holmes A, Roseaulin L, Schurra C, Waxin H, Lambert S, Zaratiegui M, Martienssen RA, Arcangioli B (2012) Lsd1 and lsd2 control programmed replication fork pauses and imprinting in fission yeast. Cell Rep 2:1513–1520

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hoshino I, Akutsu Y, Murakami K, Akanuma N, Isozaki Y, Maruyama T, Toyozumi T, Matsumoto Y, Suito H, Takahashi M, Sekino N, Komatsu A, Suzuki T, Matsubara H (2016) Histone demethylase LSD1 inhibitors prevent cell growth by regulating gene expression in esophageal squamous cell carcinoma cells. Ann Surg Oncol 23:312–320

    Article  PubMed  Google Scholar 

  • Hou H, Yu H (2010) Structural insights into histone lysine demethylation. Curr Opin Struct Biol 20:739–748

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hsu HC, Liu YS, Tseng KC, Yang TS, Yeh CY, You JF, Hung HY, Chen SJ, Chen HC (2015) CBB1003, a lysine-specific demethylase 1 inhibitor, suppresses colorectal cancer cells growth through down-regulation of leucine-rich repeat-containing G-protein-coupled receptor 5 expression. J Cancer Res Clin Oncol 141:11–21

    Article  CAS  PubMed  Google Scholar 

  • Hu X, Li X, Valverde K, Fu X, Noguchi C, Qiu Y, Huang S (2009) LSD1-mediated epigenetic modification is required for TAL1 function and hematopoiesis. Proc Natl Acad Sci USA 106:10141–10146

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huang J, Sengupta R, Espejo AB, Lee MG, Dorsey JA, Richter M, Opravil S, Shiekhattar R, Bedford MT, Jenuwein T, Berger SL (2007a) p53 is regulated by the lysine demethylase LSD1. Nature 449:105–108

    Article  CAS  PubMed  Google Scholar 

  • Huang Y, Greene E, Murray Stewart T, Goodwin AC, Baylin SB, Woster PM, Casero RA Jr (2007b) Inhibition of lysine-specific demethylase 1 by polyamine analogues results in reexpression of aberrantly silenced genes. Proc Natl Acad Sci USA 104:8023–8028

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huang M, Chen C, Geng J, Han D, Wang T, Xie T, Wang L, Wang Y, Wang C, Lei Z, Chu X (2017) Targeting KDM1A attenuates Wnt/beta-catenin signaling pathway to eliminate sorafenib-resistant stem-like cells in hepatocellular carcinoma. Cancer Lett 398:12–21

    Article  CAS  PubMed  Google Scholar 

  • Huang Y, Marton LJ, Woster PM, Casero RA (2009a) Polyamine analogues targeting epigenetic gene regulation. Essays Biochem 46:95–110

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huang Y, Stewart TM, Wu Y, Baylin SB, Marton LJ, Perkins B, Jones RJ, Woster PM, Casero RA Jr (2009b) Novel oligoamine analogues inhibit lysine-specific demethylase 1 and induce reexpression of epigenetically silenced genes. Clin Cancer Res Official J Am Assoc Cancer Res 15:7217–7228

    Article  CAS  Google Scholar 

  • Huang Y, Vasilatos SN, Boric L, Shaw PG, Davidson NE (2012) Inhibitors of histone demethylation and histone deacetylation cooperate in regulating gene expression and inhibiting growth in human breast cancer cells. Breast Cancer Res Treat 131:777–789

    Article  CAS  PubMed  Google Scholar 

  • Huang Z, Li S, Song W, Li X, Li Q, Zhang Z, Han Y, Zhang X, Miao S, Du R, Wang L (2013) Lysine-specific demethylase 1 (LSD1/KDM1A) contributes to colorectal tumorigenesis via activation of the Wnt/beta-catenin pathway by down-regulating Dickkopf-1 (DKK1) [corrected]. PLoS ONE 8:e70077

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Itoh Y, Aihara K, Mellini P, Tojo T, Ota Y, Tsumoto H, Solomon VR, Zhan P, Suzuki M, Ogasawara D, Shigenaga A, Inokuma T, Nakagawa H, Miyata N, Mizukami T, Otaka A, Suzuki T (2016) Identification of SNAIL1 peptide-based irreversible lysine-specific demethylase 1-selective inactivators. J Med Chem 59:1531–1544

    Article  CAS  PubMed  Google Scholar 

  • Jambhekar A, Anastas JN, Shi Y (2017) Histone lysine demethylase inhibitors. Cold Spring Harbor Perspect Med 7

    Google Scholar 

  • Jie D, Zhongmin Z, Guoqing L, Sheng L, Yi Z, Jing W, Liang Z (2013) Positive expression of LSD1 and negative expression of E-cadherin correlate with metastasis and poor prognosis of colon cancer. Dig Dis Sci 58:1581–1589

    Article  PubMed  Google Scholar 

  • Kahl P, Gullotti L, Heukamp LC, Wolf S, Friedrichs N, Vorreuther R, Solleder G, Bastian PJ, Ellinger J, Metzger E, Schule R, Buettner R (2006) Androgen receptor coactivators lysine-specific histone demethylase 1 and four and a half LIM domain protein 2 predict risk of prostate cancer recurrence. Can Res 66:11341–11347

    Article  CAS  Google Scholar 

  • Kakizawa T, Ota Y, Itoh Y, Tsumoto H, Suzuki T (2015) Histone H3 peptide based LSD1-selective inhibitors. Bioorg Med Chem Lett 25:1925–1928

    Article  CAS  PubMed  Google Scholar 

  • Kalyani AJ, Rao MS (1998) Cell lineage in the developing neural tube. Biochem Cell Biol 76:1051–1068

    Article  CAS  PubMed  Google Scholar 

  • Katz TA, Vasilatos SN, Harrington E, Oesterreich S, Davidson NE, Huang Y (2014) Inhibition of histone demethylase, LSD2 (KDM1B), attenuates DNA methylation and increases sensitivity to DNMT inhibitor-induced apoptosis in breast cancer cells. Breast Cancer Res Treat 146:99–108

    Article  CAS  PubMed  Google Scholar 

  • Kauffman EC, Robinson BD, Downes MJ, Powell LG, Lee MM, Scherr DS, Gudas LJ, Mongan NP (2011) Role of androgen receptor and associated lysine-demethylase coregulators, LSD1 and JMJD2A, in localized and advanced human bladder cancer. Mol Carcinog 50:931–944

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kerenyi MA, Shao Z, Hsu YJ, Guo G, Luc S, O’Brien K, Fujiwara Y, Peng C, Nguyen M, Orkin SH (2013) Histone demethylase Lsd1 represses hematopoietic stem and progenitor cell signatures during blood cell maturation. eLife 2:e00633

    Google Scholar 

  • Kim D, Kim KI, Baek SH (2021) Roles of lysine-specific demethylase 1 (LSD1) in homeostasis and diseases. J Biomed Sci 28:41

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kontaki H, Talianidis I (2010) Lysine methylation regulates E2F1-induced cell death. Mol Cell 39:152–160

    Article  CAS  PubMed  Google Scholar 

  • Latos PA, Goncalves A, Oxley D, Mohammed H, Turro E, Hemberger M (2015) Fgf and Esrrb integrate epigenetic and transcriptional networks that regulate self-renewal of trophoblast stem cells. Nat Commun 6:7776

    Article  CAS  PubMed  Google Scholar 

  • Laurent B, Ruitu L, Murn J, Hempel K, Ferrao R, Xiang Y, Liu S, Garcia BA, Wu H, Wu F, Steen H, Shi Y (2015) A specific LSD1/KDM1A isoform regulates neuronal differentiation through H3K9 demethylation. Mol Cell 57:957–970

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee MG, Norman J, Shilatifard A, Shiekhattar R (2007) Physical and functional association of a trimethyl H3K4 demethylase and Ring6a/MBLR, a polycomb-like protein. Cell 128:877–887

    Article  CAS  PubMed  Google Scholar 

  • Lee MG, Wynder C, Cooch N, Shiekhattar R (2005) An essential role for CoREST in nucleosomal histone 3 lysine 4 demethylation. Nature 437:432–435

    Article  CAS  PubMed  Google Scholar 

  • Lee MG, Wynder C, Schmidt DM, McCafferty DG, Shiekhattar R (2006) Histone H3 lysine 4 demethylation is a target of nonselective antidepressive medications. Chem Biol 13:563–567

    Article  CAS  PubMed  Google Scholar 

  • Li Y, Deng C, Hu X, Patel B, Fu X, Qiu Y, Brand M, Zhao K, Huang S (2012) Dynamic interaction between TAL1 oncoprotein and LSD1 regulates TAL1 function in hematopoiesis and leukemogenesis. Oncogene 31:5007–5018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li Y, Tian X, Sui CG, Jiang YH, Liu YP, Meng FD (2016) Interference of lysine-specific demethylase 1 inhibits cellular invasion and proliferation in vivo in gastric cancer MKN-28 cells. Biomed Pharmacother 82:498–508

    Article  CAS  PubMed  Google Scholar 

  • Liang Y, Ahmed M, Guo H, Soares F, Hua JT, Gao S, Lu C, Poon C, Han W, Langstein J, Ekram MB, Li B, Davicioni E, Takhar M, Erho N, Karnes RJ, Chadwick D, van der Kwast T, Boutros PC, Arrowsmith CH, Feng FY, Joshua AM, Zoubeidi A, Cai C, He HH (2017) LSD1-mediated epigenetic reprogramming drives CENPE expression and prostate cancer progression. Can Res 77:5479–5490

    Article  CAS  Google Scholar 

  • Liang Y, Quenelle D, Vogel JL, Mascaro C, Ortega A, Kristie TM (2013) A novel selective LSD1/KDM1A inhibitor epigenetically blocks herpes simplex virus lytic replication and reactivation from latency. mBio 4:e00558-00512

    Google Scholar 

  • Lim S, Janzer A, Becker A, Zimmer A, Schule R, Buettner R, Kirfel J (2010) Lysine-specific demethylase 1 (LSD1) is highly expressed in ER-negative breast cancers and a biomarker predicting aggressive biology. Carcinogenesis 31:512–520

    Article  CAS  PubMed  Google Scholar 

  • Lin T, Ponn A, Hu X, Law BK, Lu J (2010a) Requirement of the histone demethylase LSD1 in Snai1-mediated transcriptional repression during epithelial-mesenchymal transition. Oncogene 29:4896–4904

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lin Y, Wu Y, Li J, Dong C, Ye X, Chi YI, Evers BM, Zhou BP (2010b) The SNAG domain of Snail1 functions as a molecular hook for recruiting lysine-specific demethylase 1. EMBO J 29:1803–1816

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu L, Souto J, Liao W, Jiang Y, Li Y, Nishinakamura R, Huang S, Rosengart T, Yang VW, Schuster M, Ma Y, Yang J (2013) Histone lysine-specific demethylase 1 (LSD1) protein is involved in Sal-like protein 4 (SALL4)-mediated transcriptional repression in hematopoietic stem cells. J Biol Chem 288:34719–34728

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu Y, Debo B, Li M, Shi Z, Sheng W, Shi Y (2021) LSD1 inhibition sustains T cell invigoration with a durable response to PD-1 blockade. Nat Commun 12:6831

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lokken AA, Zeleznik-Le NJ (2012) Breaking the LSD1/KDM1A addiction: therapeutic targeting of the epigenetic modifier in AML. Cancer Cell 21:451–453

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lopez CI, Saud KE, Aguilar R, Berndt FA, Canovas J, Montecino M, Kukuljan M (2016) The chromatin modifying complex CoREST/LSD1 negatively regulates notch pathway during cerebral cortex development. Dev Neurobiol 76:1360–1373

    Article  CAS  PubMed  Google Scholar 

  • Lu J, McKinsey TA, Zhang CL, Olson EN (2000) Regulation of skeletal myogenesis by association of the MEF2 transcription factor with class II histone deacetylases. Mol Cell 6:233–244

    Article  CAS  PubMed  Google Scholar 

  • Lv T, Yuan D, Miao X, Lv Y, Zhan P, Shen X, Song Y (2012) Over-expression of LSD1 promotes proliferation, migration and invasion in non-small cell lung cancer. PLoS ONE 7:e35065

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lynch JT, Harris WJ, Somervaille TC (2012) LSD1 inhibition: a therapeutic strategy in cancer? Expert Opin Ther Targets 16:1239–1249

    Article  CAS  PubMed  Google Scholar 

  • Maiques-Diaz A, Somervaille TC (2016) LSD1: biologic roles and therapeutic targeting. Epigenomics 8:1103–1116

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mal A, Harter ML (2003) MyoD is functionally linked to the silencing of a muscle-specific regulatory gene prior to skeletal myogenesis. Proc Natl Acad Sci USA 100:1735–1739

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Metzger E, Wissmann M, Yin N, Muller JM, Schneider R, Peters AH, Gunther T, Buettner R, Schule R (2005) LSD1 demethylates repressive histone marks to promote androgen-receptor-dependent transcription. Nature 437:436–439

    Article  CAS  PubMed  Google Scholar 

  • Mimasu S, Umezawa N, Sato S, Higuchi T, Umehara T, Yokoyama S (2010) Structurally designed trans-2-phenylcyclopropylamine derivatives potently inhibit histone demethylase LSD1/KDM1. Biochemistry 49:6494–6503

    Article  CAS  PubMed  Google Scholar 

  • Mohammad HP, Kruger RG (2016) Antitumor activity of LSD1 inhibitors in lung cancer. Molecular Cell Oncol 3:e1117700

    Article  Google Scholar 

  • Mohammad HP, Smitheman KN, Kamat CD, Soong D, Federowicz KE, Van Aller GS, Schneck JL, Carson JD, Liu Y, Butticello M, Bonnette WG, Gorman SA, Degenhardt Y, Bai Y, McCabe MT, Pappalardi MB, Kasparec J, Tian X, McNulty KC, Rouse M, McDevitt P, Ho T, Crouthamel M, Hart TK, Concha NO, McHugh CF, Miller WH, Dhanak D, Tummino PJ, Carpenter CL, Johnson NW, Hann CL, Kruger RG (2015) A DNA hypomethylation signature predicts antitumor activity of LSD1 inhibitors in SCLC. Cancer Cell 28:57–69

    Article  CAS  PubMed  Google Scholar 

  • Molkentin JD, Olson EN (1996) Defining the regulatory networks for muscle development. Curr Opin Genet Dev 6:445–453

    Article  CAS  PubMed  Google Scholar 

  • Morera L, Lubbert M, Jung M (2016) Targeting histone methyltransferases and demethylases in clinical trials for cancer therapy. Clin Epigenetics 8:57

    Article  PubMed  PubMed Central  Google Scholar 

  • Mulligan P, Yang F, Di Stefano L, Ji JY, Ouyang J, Nishikawa JL, Toiber D, Kulkarni M, Wang Q, Najafi-Shoushtari SH, Mostoslavsky R, Gygi SP, Gill G, Dyson NJ, Naar AM (2011) A SIRT1-LSD1 corepressor complex regulates Notch target gene expression and development. Mol Cell 42:689–699

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Murray-Stewart T, Woster PM, Casero RA (2013) The re-expression of the epigenetically silenced e-cadherin gene by a polyamine analogue lysine-specific demethylase-1 (LSD1) inhibitor in human acute myeloid leukemia cell lines. Amino Acids 46:585–594

    Article  PubMed  PubMed Central  Google Scholar 

  • Musella M, Guarracino A, Manduca N, Galassi C, Ruggiero E, Potenza A, Maccafeo E, Manic G, Mattiello L, Soliman Abdel Rehim S, Signore M, Pietrosanto M, Helmer-Citterich M, Pallocca M, Fanciulli M, Bruno T, De Nicola F, Corleone G, Di Benedetto A, Ercolani C, Pescarmona E, Pizzuti L, Guidi F, Sperati F, Vitale S, Macchia D, Spada M, Schiavoni G, Mattei F, De Ninno A, Businaro L, Lucarini V, Bracci L, Arico E, Ziccheddu G, Facchiano F, Rossi S, Sanchez M, Boe A, Biffoni M, De Maria R, Vitale I, Sistigu A (2022) Type I IFNs promote cancer cell stemness by triggering the epigenetic regulator KDM1B. Nat Immunol 23:1379–1392

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Musri MM, Carmona MC, Hanzu FA, Kaliman P, Gomis R, Parrizas M (2010) Histone demethylase LSD1 regulates adipogenesis. J Biol Chem 285:30034–30041

    Article  PubMed  PubMed Central  Google Scholar 

  • Nagaoka K, Hino S, Sakamoto A, Anan K, Takase R, Umehara T, Yokoyama S, Sasaki Y, Nakao M (2015) Lysine-specific demethylase 2 suppresses lipid influx and metabolism in hepatic cells. Mol Cell Biol 35:1068–1080

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nair SS, Li DQ, Kumar R (2013) A core chromatin remodeling factor instructs global chromatin signaling through multivalent reading of nucleosome codes. Mol Cell 49:704–718

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Neelamegam R, Ricq EL, Malvaez M, Patnaik D, Norton S, Carlin SM, Hill IT, Wood MA, Haggarty SJ, Hooker JM (2012) Brain-penetrant LSD1 inhibitors can block memory consolidation. ACS Chem Neurosci 3:120–128

    Article  CAS  PubMed  Google Scholar 

  • Nguyen EM, Taniguchi H, Chan JM, Zhan YA, Chen X, Qiu J, de Stanchina E, Allaj V, Shah NS, Uddin F, Manoj P, Liu M, Cai SF, Levine R, Quintanal-Villalonga A, Sen T, Chow A, Rudin CM (2022) Targeting lysine-specific demethylase 1 rescues major histocompatibility complex class I antigen presentation and overcomes programmed death-ligand 1 blockade resistance in SCLC. J Thorac Oncol 17:1014–1031

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nicholson TB, Chen T (2014) LSD1 demethylates histone and non-histone proteins. Epigenetics 4:129–132

    Article  Google Scholar 

  • Nikoloski G, Langemeijer SM, Kuiper RP, Knops R, Massop M, Tonnissen ER, van der Heijden A, Scheele TN, Vandenberghe P, de Witte T, van der Reijden BA, Jansen JH (2010) Somatic mutations of the histone methyltransferase gene EZH2 in myelodysplastic syndromes. Nat Genet 42:665–667

    Article  CAS  PubMed  Google Scholar 

  • Nowak RP, Tumber A, Johansson C, Che KH, Brennan P, Owen D, Oppermann U (2016) Advances and challenges in understanding histone demethylase biology. Curr Opin Chem Biol 33:151–159

    Article  CAS  PubMed  Google Scholar 

  • Nowotarski SL, Pachaiyappan B, Holshouser SL, Kutz CJ, Li Y, Huang Y, Sharma SK, Casero RA Jr, Woster PM (2015) Structure-activity study for (bis)ureidopropyl- and (bis)thioureidopropyldiamine LSD1 inhibitors with 3-5-3 and 3-6-3 carbon backbone architectures. Bioorg Med Chem 23:1601–1612

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ogasawara D, Suzuki T, Mino K, Ueda R, Khan MN, Matsubara T, Koseki K, Hasegawa M, Sasaki R, Nakagawa H, Mizukami T, Miyata N (2011) Synthesis and biological activity of optically active NCL-1, a lysine-specific demethylase 1 selective inhibitor. Bioorg Med Chem 19:3702–3708

    Article  CAS  PubMed  Google Scholar 

  • Ombra MN, Di Santi A, Abbondanza C, Migliaccio A, Avvedimento EV, Perillo B (2013) Retinoic acid impairs estrogen signaling in breast cancer cells by interfering with activation of LSD1 via PKA. Biochem Biophys Acta 1829:480–486

    CAS  PubMed  Google Scholar 

  • Ota Y, Itoh Y, Kaise A, Ohta K, Endo Y, Masuda M, Sowa Y, Sakai T, Suzuki T (2016) Targeting cancer with PCPA-drug conjugates: LSD1 inhibition-triggered release of 4-hydroxytamoxifen. Angew Chem 55:16115–16118

    Article  CAS  Google Scholar 

  • Ouyang J, Shi Y, Valin A, Xuan Y, Gill G (2009) Direct binding of CoREST1 to SUMO-2/3 contributes to gene-specific repression by the LSD1/CoREST1/HDAC complex. Mol Cell 34:145–154

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pastor WA, Aravind L, Rao A (2013) TETonic shift: biological roles of TET proteins in DNA demethylation and transcription. Nat Rev Mol Cell Biol 14:341–356

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Perillo B, Tramontano A, Pezone A, Migliaccio A (2020) LSD1: more than demethylation of histone lysine residues. Exp Mol Med 52:1936–1947

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pollock JA, Larrea MD, Jasper JS, McDonnell DP, McCafferty DG (2012) Lysine-specific histone demethylase 1 inhibitors control breast cancer proliferation in ERalpha-dependent and -independent manners. ACS Chem Biol 7:1221–1231

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Prusevich P, Kalin JH, Ming SA, Basso M, Givens J, Li X, Hu J, Taylor MS, Cieniewicz AM, Hsiao PY, Huang R, Roberson H, Adejola N, Avery LB, Casero RA Jr, Taverna SD, Qian J, Tackett AJ, Ratan RR, McDonald OG, Feinberg AP, Cole PA (2014) A selective phenelzine analogue inhibitor of histone demethylase LSD1. ACS Chem Biol 9:1284–1293

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ray SK, Li HJ, Metzger E, Schule R, Leiter AB (2014) CtBP and associated LSD1 are required for transcriptional activation by NeuroD1 in gastrointestinal endocrine cells. Mol Cell Biol 34:2308–2317

    Article  PubMed  PubMed Central  Google Scholar 

  • Reitman ZJ, Jin G, Karoly ED, Spasojevic I, Yang J, Kinzler KW, He Y, Bigner DD, Vogelstein B, Yan H (2011) Profiling the effects of isocitrate dehydrogenase 1 and 2 mutations on the cellular metabolome. Proc Natl Acad Sci USA 108:3270–3275

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ribeiro AF, Pratcorona M, Erpelinck-Verschueren C, Rockova V, Sanders M, Abbas S, Figueroa ME, Zeilemaker A, Melnick A, Lowenberg B, Valk PJ, Delwel R (2012) Mutant DNMT3A: a marker of poor prognosis in acute myeloid leukemia. Blood 119:5824–5831

    Article  CAS  PubMed  Google Scholar 

  • Rotili D, Tomassi S, Conte M, Benedetti R, Tortorici M, Ciossani G, Valente S, Marrocco B, Labella D, Novellino E, Mattevi A, Altucci L, Tumber A, Yapp C, King ON, Hopkinson RJ, Kawamura A, Schofield CJ, Mai A (2014) Pan-histone demethylase inhibitors simultaneously targeting Jumonji C and lysine-specific demethylases display high anticancer activities. J Med Chem 57:42–55

    Article  CAS  PubMed  Google Scholar 

  • Russler-Germain DA, Spencer DH, Young MA, Lamprecht TL, Miller CA, Fulton R, Meyer MR, Erdmann-Gilmore P, Townsend RR, Wilson RK, Ley TJ (2014) The R882H DNMT3A mutation associated with AML dominantly inhibits wild-type DNMT3A by blocking its ability to form active tetramers. Cancer Cell 25:442–454

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Saez JE, Gomez AV, Barrios AP, Parada GE, Galdames L, Gonzalez M, Andres ME (2015) Decreased expression of CoREST1 and CoREST2 together with LSD1 and HDAC1/2 during neuronal differentiation. PLoS ONE 10:e0131760

    Article  PubMed  PubMed Central  Google Scholar 

  • Sambeat A, Gulyaeva O, Dempersmier J, Tharp KM, Stahl A, Paul SM, Sul HS (2016) LSD1 interacts with Zfp516 to promote UCP1 transcription and brown fat program. Cell Rep 15:2536–2549

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sankar S, Bell R, Stephens B, Zhuo R, Sharma S, Bearss DJ, Lessnick SL (2013) Mechanism and relevance of EWS/FLI-mediated transcriptional repression in Ewing sarcoma. Oncogene 32:5089–5100

    Article  CAS  PubMed  Google Scholar 

  • Sareddy GR, Nair BC, Krishnan SK, Gonugunta VK, Zhang QG, Suzuki T, Miyata N, Brenner AJ, Brann DW, Vadlamudi RK (2013) KDM1 is a novel therapeutic target for the treatment of gliomas. Oncotarget 4:18–28

    Article  PubMed  Google Scholar 

  • Schenk T, Chen WC, Gollner S, Howell L, Jin L, Hebestreit K, Klein HU, Popescu AC, Burnett A, Mills K, Casero RA Jr, Marton L, Woster P, Minden MD, Dugas M, Wang JC, Dick JE, Muller-Tidow C, Petrie K, Zelent A (2012) Inhibition of the LSD1 (KDM1A) demethylase reactivates the all-trans-retinoic acid differentiation pathway in acute myeloid leukemia. Nat Med 18:605–611

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schmidt DM, McCafferty DG (2007) Trans-2-phenylcyclopropylamine is a mechanism-based inactivator of the histone demethylase LSD1. Biochemistry 46:4408–4416

    Article  CAS  PubMed  Google Scholar 

  • Schmitt ML, Hauser AT, Carlino L, Pippel M, Schulz-Fincke J, Metzger E, Willmann D, Yiu T, Barton M, Schule R, Sippl W, Jung M (2013) Nonpeptidic propargylamines as inhibitors of lysine specific demethylase 1 (LSD1) with cellular activity. J Med Chem 56:7334–7342

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schulte JH, Lim S, Schramm A, Friedrichs N, Koster J, Versteeg R, Ora I, Pajtler K, Klein-Hitpass L, Kuhfittig-Kulle S, Metzger E, Schule R, Eggert A, Buettner R, Kirfel J (2009) Lysine-specific demethylase 1 is strongly expressed in poorly differentiated neuroblastoma: implications for therapy. Cancer Res 69:2065–2071

    Article  CAS  PubMed  Google Scholar 

  • Scionti I, Hayashi S, Mouradian S, Girard E, Esteves de Lima J, Morel V, Simonet T, Wurmser M, Maire P, Ancelin K, Metzger E, Schule R, Goillot E, Relaix F, Schaeffer L (2017) LSD1 controls timely MyoD expression via MyoD core enhancer transcription. Cell Rep 18:1996–2006

    Article  CAS  PubMed  Google Scholar 

  • Scoumanne A, Chen X (2007) The lysine-specific demethylase 1 is required for cell proliferation in both p53-dependent and -independent manners. J Biol Chem 282:15471–15475

    Article  CAS  PubMed  Google Scholar 

  • Sehrawat A, Gao L, Wang Y, Bankhead A 3rd, McWeeney SK, King CJ, Schwartzman J, Urrutia J, Bisson WH, Coleman DJ, Joshi SK, Kim DH, Sampson DA, Weinmann S, Kallakury BVS, Berry DL, Haque R, Van Den Eeden SK, Sharma S, Bearss J, Beer TM, Thomas GV, Heiser LM, Alumkal JJ (2018) LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci USA 115:E4179–E4188

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shao GB, Huang XJ, Gong AH, Zhang ZJ, Lu RZ, Sang JR (2010) Histone demethylase LSD1 and its biological functions. Yi Chuan 32:331–338

    Article  CAS  PubMed  Google Scholar 

  • Sharma SK, Wu Y, Steinbergs N, Crowley ML, Hanson AS, Casero RA, Woster PM (2010) (Bis)urea and (bis)thiourea inhibitors of lysine-specific demethylase 1 as epigenetic modulators. J Med Chem 53:5197–5212

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sheng W, LaFleur MW, Nguyen TH, Chen S, Chakravarthy A, Conway JR, Li Y, Chen H, Yang H, Hsu PH, Van Allen EM, Freeman GJ, De Carvalho DD, He HH, Sharpe AH, Shi Y (2018) LSD1 ablation stimulates anti-tumor immunity and enables checkpoint blockade. Cell 174(549–563):e519

    Google Scholar 

  • Sheng W, Liu Y, Chakraborty D, Debo B, Shi Y (2021) Simultaneous inhibition of LSD1 and TGFbeta enables eradication of poorly immunogenic tumors with anti-PD-1 treatment. Cancer Discov 11:1970–1981

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shi Y, Lan F, Matson C, Mulligan P, Whetstine JR, Cole PA, Casero RA, Shi Y (2004) Histone demethylation mediated by the nuclear amine oxidase homolog LSD1. Cell 119:941–953

    Article  CAS  PubMed  Google Scholar 

  • Shi Y, Sawada J, Sui G, el Affar B, Whetstine JR, Lan F, Ogawa H, Luke MP, Nakatani Y, Shi Y (2003) Coordinated histone modifications mediated by a CtBP co-repressor complex. Nature 422:735–738

    Article  CAS  PubMed  Google Scholar 

  • Shi YG, Tsukada Y (2013) The discovery of histone demethylases. Cold Spring Harbor Perspect Biol 5

    Google Scholar 

  • Shi YJ, Matson C, Lan F, Iwase S, Baba T, Shi Y (2005) Regulation of LSD1 histone demethylase activity by its associated factors. Mol Cell 19:857–864

    Article  CAS  PubMed  Google Scholar 

  • Song Y, Zhang H, Yang X, Shi Y, Yu B (2022) Annual review of lysine-specific demethylase 1 (LSD1/KDM1A) inhibitors in 2021. Euro J Med Chem 228

    Google Scholar 

  • Sonnemann J, Zimmermann M, Marx C, Ebert F, Becker S, Lauterjung ML, Beck JF (2017) LSD1 (KDM1A)-independent effects of the LSD1 inhibitor SP2509 in cancer cells. Br J Haematol

    Google Scholar 

  • Sorna V, Theisen ER, Stephens B, Warner SL, Bearss DJ, Vankayalapati H, Sharma S (2013) High-throughput virtual screening identifies novel N’-(1-phenylethylidene)-benzohydrazides as potent, specific, and reversible LSD1 inhibitors. J Med Chem 56:9496–9508

    Article  CAS  PubMed  Google Scholar 

  • Sprussel A, Schulte JH, Weber S, Necke M, Handschke K, Thor T, Pajtler KW, Schramm A, Konig K, Diehl L, Mestdagh P, Vandesompele J, Speleman F, Jastrow H, Heukamp LC, Schule R, Duhrsen U, Buettner R, Eggert A, Gothert JR (2012) Lysine-specific demethylase 1 restricts hematopoietic progenitor proliferation and is essential for terminal differentiation. Leukemia 26:2039–2051

    Article  CAS  PubMed  Google Scholar 

  • Stavropoulos P, Blobel G, Hoelz A (2006) Crystal structure and mechanism of human lysine-specific demethylase-1. Nat Struct Mol Biol 13:626–632

    Article  CAS  PubMed  Google Scholar 

  • Stazi G, Zwergel C, Valente S, Mai A (2016) LSD1 inhibitors: a patent review (2010–2015). Expert Opin Ther Pat 26:565–580

    Article  CAS  PubMed  Google Scholar 

  • Steinbac OC, Wolffe AP, Rupp RA (2000) Histone deacetylase activity is required for the induction of the MyoD muscle cell lineage in Xenopus. Biol Chem 381:1013–1016

    CAS  PubMed  Google Scholar 

  • Stewart CA, Byers LA (2015) Altering the course of small cell lung cancer: targeting cancer stem cells via LSD1 inhibition. Cancer Cell 28:4–6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stewart KR, Veselovska L, Kim J, Huang J, Saadeh H, Tomizawa S, Smallwood SA, Chen T, Kelsey G (2015) Dynamic changes in histone modifications precede de novo DNA methylation in oocytes. Genes Dev 29:2449–2462

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Straub LG, Wolfrum C (2017) LSD1 makes fat colorful. Trends Endocrinol Metab 28:1–2

    Article  CAS  PubMed  Google Scholar 

  • Sun G, Alzayady K, Stewart R, Ye P, Yang S, Li W, Shi Y (2010) Histone demethylase LSD1 regulates neural stem cell proliferation. Mol Cell Biol 30:1997–2005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sun G, Ye P, Murai K, Lang MF, Li S, Zhang H, Li W, Fu C, Yin J, Wang A, Ma X, Shi Y (2011) miR-137 forms a regulatory loop with nuclear receptor TLX and LSD1 in neural stem cells. Nat Commun 2:529

    Article  PubMed  Google Scholar 

  • Sun L, Fang J (2016) Epigenetic regulation of epithelial-mesenchymal transition. Cell Mole Life Sci CMLS 73:4493–4515

    Article  CAS  Google Scholar 

  • Taylor MV, Hughes SM (2017) Mef2 and the skeletal muscle differentiation program. Semin Cell Dev Biol 72:33–44

    Article  CAS  PubMed  Google Scholar 

  • Topper MJ (2017) Leading the way in veterinary research; acknowledging these passionate professionals. J Am Vet Med Assoc 251:478

    Article  PubMed  Google Scholar 

  • Tortorici M, Borrello MT, Tardugno M, Chiarelli LR, Pilotto S, Ciossani G, Vellore NA, Bailey SG, Cowan J, O’Connell M, Crabb SJ, Packham G, Mai A, Baron R, Ganesan A, Mattevi A (2013) Protein recognition by short peptide reversible inhibitors of the chromatin-modifying LSD1/CoREST lysine demethylase. ACS Chem Biol 8:1677–1682

    Article  CAS  PubMed  Google Scholar 

  • Tsukada Y, Fang J, Erdjument-Bromage H, Warren ME, Borchers CH, Tempst P, Zhang Y (2006) Histone demethylation by a family of JmjC domain-containing proteins. Nature 439:811–816

    Article  CAS  PubMed  Google Scholar 

  • Ueda R, Suzuki T, Mino K, Tsumoto H, Nakagawa H, Hasegawa M, Sasaki R, Mizukami T, Miyata N (2009) Identification of cell-active lysine specific demethylase 1-selective inhibitors. J Am Chem Soc 131:17536–17537

    Article  CAS  PubMed  Google Scholar 

  • Urban N, Guillemot F (2014) Neurogenesis in the embryonic and adult brain: same regulators, different roles. Front Cell Neurosci 8:396

    Article  PubMed  PubMed Central  Google Scholar 

  • Vasilatos SN, Katz TA, Oesterreich S, Wan Y, Davidson NE, Huang Y (2013) Crosstalk between lysine-specific demethylase 1 (LSD1) and histone deacetylases mediates antineoplastic efficacy of HDAC inhibitors in human breast cancer cells. Carcinogenesis 34:1196–1207

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vianello P, Botrugno OA, Cappa A, Ciossani G, Dessanti P, Mai A, Mattevi A, Meroni G, Minucci S, Thaler F, Tortorici M, Trifiro P, Valente S, Villa M, Varasi M, Mercurio C (2014) Synthesis, biological activity and mechanistic insights of 1-substituted cyclopropylamine derivatives: a novel class of irreversible inhibitors of histone demethylase KDM1A. Eur J Med Chem 86:352–363

    Article  CAS  PubMed  Google Scholar 

  • Vianello P, Botrugno OA, Cappa A, Dal Zuffo R, Dessanti P, Mai A, Marrocco B, Mattevi A, Meroni G, Minucci S, Stazi G, Thaler F, Trifiro P, Valente S, Villa M, Varasi M, Mercurio C (2016) Discovery of a novel inhibitor of histone lysine-specific demethylase 1A (KDM1A/LSD1) as orally active antitumor agent. J Med Chem 59:1501–1517

    Article  CAS  PubMed  Google Scholar 

  • Wang J, Hevi S, Kurash JK, Lei H, Gay F, Bajko J, Su H, Sun W, Chang H, Xu G, Gaudet F, Li E, Chen T (2008) The lysine demethylase LSD1 (KDM1) is required for maintenance of global DNA methylation. Nat Genet 41:125–129

    Article  PubMed  Google Scholar 

  • Wang J, Hevi S, Kurash JK, Lei H, Gay F, Bajko J, Su H, Sun W, Chang H, Xu G, Gaudet F, Li E, Chen T (2009a) The lysine demethylase LSD1 (KDM1) is required for maintenance of global DNA methylation. Nat Genet 41:125–129

    Article  CAS  PubMed  Google Scholar 

  • Wang J, Lu F, Ren Q, Sun H, Xu Z, Lan R, Liu Y, Ward D, Quan J, Ye T, Zhang H (2011) Novel histone demethylase LSD1 inhibitors selectively target cancer cells with pluripotent stem cell properties. Can Res 71:7238–7249

    Article  CAS  Google Scholar 

  • Wang J, Scully K, Zhu X, Cai L, Zhang J, Prefontaine GG, Krones A, Ohgi KA, Zhu P, Garcia-Bassets I, Liu F, Taylor H, Lozach J, Jayes FL, Korach KS, Glass CK, Fu XD, Rosenfeld MG (2007) Opposing LSD1 complexes function in developmental gene activation and repression programmes. Nature 446:882–887

    Article  CAS  PubMed  Google Scholar 

  • Wang M, Liu X, Guo J, Weng X, Jiang G, Wang Z, He L (2015) Inhibition of LSD1 by pargyline inhibited process of EMT and delayed progression of prostate cancer in vivo. Biochem Biophys Res Commun 467:310–315

    Article  CAS  PubMed  Google Scholar 

  • Wang Y, Wu Q, Yang P, Wang C, Liu J, Ding W, Liu W, Bai Y, Yang Y, Wang H, Gao S, Wang X (2016) LSD1 co-repressor Rcor2 orchestrates neurogenesis in the developing mouse brain. Nat Commun 7:10481

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang Y, Zhang H, Chen Y, Sun Y, Yang F, Yu W, Liang J, Sun L, Yang X, Shi L, Li R, Li Y, Zhang Y, Li Q, Yi X, Shang Y (2009b) LSD1 is a subunit of the NuRD complex and targets the metastasis programs in breast cancer. Cell 138:660–672

    Article  CAS  PubMed  Google Scholar 

  • Wei X, Calvo-Vidal MN, Chen S, Wu G, Revuelta MV, Sun J, Zhang J, Walsh MF, Nichols KE, Joseph V, Snyder C, Vachon CM, McKay JD, Wang SP, Jayabalan DS, Jacobs LM, Becirovic D, Waller RG, Artomov M, Viale A, Patel J, Phillip J, Chen-Kiang S, Curtin K, Salama M, Atanackovic D, Niesvizky R, Landgren O, Slager SL, Godley LA, Churpek J, Garber JE, Anderson KC, Daly MJ, Roeder RG, Dumontet C, Lynch HT, Mullighan CG, Camp NJ, Offit K, Klein RJ, Yu H, Cerchietti L, Lipkin SM (2018) Germline lysine-specific demethylase 1 (LSD1/KDM1A) mutations confer susceptibility to multiple myeloma. Can Res 78:2747–2759

    Article  CAS  Google Scholar 

  • Whyte WA, Bilodeau S, Orlando DA, Hoke HA, Frampton GM, Foster CT, Cowley SM, Young RA (2012) Enhancer decommissioning by LSD1 during embryonic stem cell differentiation. Nature 482:221–225

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Willmann D, Lim S, Wetzel S, Metzger E, Jandausch A, Wilk W, Jung M, Forne I, Imhof A, Janzer A, Kirfel J, Waldmann H, Schule R, Buettner R (2012) Impairment of prostate cancer cell growth by a selective and reversible lysine-specific demethylase 1 inhibitor. Int J Cancer 131:2704–2709

    Article  CAS  PubMed  Google Scholar 

  • Wissmann M, Yin N, Muller JM, Greschik H, Fodor BD, Jenuwein T, Vogler C, Schneider R, Gunther T, Buettner R, Metzger E, Schule R (2007) Cooperative demethylation by JMJD2C and LSD1 promotes androgen receptor-dependent gene expression. Nat Cell Biol 9:347–353

    Article  CAS  PubMed  Google Scholar 

  • Wu CY, Hsieh CY, Huang KE, Chang C, Kang HY (2012) Cryptotanshinone down-regulates androgen receptor signaling by modulating lysine-specific demethylase 1 function. Int J Cancer 131:1423–1434

    Article  CAS  PubMed  Google Scholar 

  • Xu G, Xiao Y, Hu J, Xing L, Zhao O, Wu Y (2013) The combined effect of retinoic acid and LSD1 siRNA inhibition on cell death in the human neuroblastoma cell line SH-SY5Y. Cell Physiol Biochem Int J Exper Cell Physiol Biochem Pharmacol 31:854–862

    Article  CAS  Google Scholar 

  • Yan HJ, Zhou SY, Li Y, Zhang H, Deng CY, Qi H, Li FR (2016) The effects of LSD1 inhibition on self-renewal and differentiation of human induced pluripotent stem cells. Exp Cell Res 340:227–237

    Article  CAS  PubMed  Google Scholar 

  • Yan XJ, Xu J, Gu ZH, Pan CM, Lu G, Shen Y, Shi JY, Zhu YM, Tang L, Zhang XW, Liang WX, Mi JQ, Song HD, Li KQ, Chen Z, Chen SJ (2011) Exome sequencing identifies somatic mutations of DNA methyltransferase gene DNMT3A in acute monocytic leukemia. Nat Genet 43:309–315

    Article  CAS  PubMed  Google Scholar 

  • Yang J, Huang J, Dasgupta M, Sears N, Miyagi M, Wang B, Chance MR, Chen X, Du Y, Wang Y, An L, Wang Q, Lu T, Zhang X, Wang Z, Stark GR (2010a) Reversible methylation of promoter-bound STAT3 by histone-modifying enzymes. Proc Natl Acad Sci USA 107:21499–21504

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang M, Gocke CB, Luo X, Borek D, Tomchick DR, Machius M, Otwinowski Z, Yu H (2006) Structural basis for CoREST-dependent demethylation of nucleosomes by the human LSD1 histone demethylase. Mol Cell 23:377–387

    Article  CAS  PubMed  Google Scholar 

  • Yang Y, Yin X, Yang H, Xu Y (2015) Histone demethylase LSD2 acts as an E3 ubiquitin ligase and inhibits cancer cell growth through promoting proteasomal degradation of OGT. Mol Cell 58:47–59

    Article  CAS  PubMed  Google Scholar 

  • Yang Z, Jiang J, Stewart MD, Qi S, Yamane K, Li J, Zhang Y, Wong J (2010b) AOF1 is a histone H3K4 demethylase possessing demethylase activity-independent repression function. Cell Res 20:276–287

    Article  CAS  PubMed  Google Scholar 

  • Yokoyama A, Takezawa S, Schule R, Kitagawa H, Kato S (2008) Transrepressive function of TLX requires the histone demethylase LSD1. Mol Cell Biol 28:3995–4003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yu Y, Wang B, Zhang K, Lei Z, Guo Y, Xiao H, Wang J, Fan L, Lan C, Wei Y, Ma Q, Lin L, Mao C, Yang X, Chen X, Li Y, Bai Y, Chen D (2013) High expression of lysine-specific demethylase 1 correlates with poor prognosis of patients with esophageal squamous cell carcinoma. Biochem Biophys Res Commun 437:192–198

    Article  CAS  PubMed  Google Scholar 

  • Zeng X, Jedrychowski MP, Chen Y, Serag S, Lavery GG, Gygi SP, Spiegelman BM (2016) Lysine-specific demethylase 1 promotes brown adipose tissue thermogenesis via repressing glucocorticoid activation. Genes Dev 30:1822–1836

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang Q, Qi S, Xu M, Yu L, Tao Y, Deng Z, Wu W, Li J, Chen Z, Wong J (2013) Structure-function analysis reveals a novel mechanism for regulation of histone demethylase LSD2/AOF1/KDM1b. Cell Res 23:225–241

    Article  CAS  PubMed  Google Scholar 

  • Zhang RH, Judson RN, Liu DY, Kast J, Rossi FM (2016) The lysine methyltransferase Ehmt2/G9a is dispensable for skeletal muscle development and regeneration. Skelet Muscle 6:22

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhang W, Ruan X, Li Y, Zhi J, Hu L, Hou X, Shi X, Wang X, Wang J, Ma W, Gu P, Zheng X, Gao M (2022a) KDM1A promotes thyroid cancer progression and maintains stemness through the Wnt/beta-catenin signaling pathway. Theranostics 12:1500–1517

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang X, Wang X, Wu T, Yin W, Yan J, Sun Y, Zhao D (2022b) Therapeutic potential of targeting LSD1/ KDM1A in cancers. Pharmacol Res 175:105958

    Article  CAS  PubMed  Google Scholar 

  • Zheng YC, Duan YC, Ma JL, Xu RM, Zi X, Lv WL, Wang MM, Ye XW, Zhu S, Mobley D, Zhu YY, Wang JW, Li JF, Wang ZR, Zhao W, Liu HM (2013) Triazole-dithiocarbamate based selective lysine specific demethylase 1 (LSD1) inactivators inhibit gastric cancer cell growth, invasion, and migration. J Med Chem 56:8543–8560

    Article  CAS  PubMed  Google Scholar 

  • Zheng YC, Ma J, Wang Z, Li J, Jiang B, Zhou W, Shi X, Wang X, Zhao W, Liu HM (2015) A systematic review of histone lysine-specific demethylase 1 and its inhibitors. Med Res Rev 35:1032–1071

    Article  CAS  PubMed  Google Scholar 

  • Zhou C, Kang D, Xu Y, Zhang L, Zha X (2015) Identification of novel selective lysine-specific demethylase 1 (LSD1) inhibitors using a pharmacophore-based virtual screening combined with docking. Chem Biol Drug Des 85:659–671

    Article  CAS  PubMed  Google Scholar 

  • Zhou C, Wu F, Lu L, Wei L, Pai E, Yao Y, Song Y (2017) Structure activity relationship and modeling studies of inhibitors of lysine specific demethylase 1. PLoS ONE 12:e0170301

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhou G, Du T, Roizman B (2013) The role of the CoREST/REST repressor complex in herpes simplex virus 1 productive infection and in latency. Viruses 5:1208–1218

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhu D, Holz S, Metzger E, Pavlovic M, Jandausch A, Jilg C, Galgoczy P, Herz C, Moser M, Metzger D, Gunther T, Arnold SJ, Schule R (2014) Lysine-specific demethylase 1 regulates differentiation onset and migration of trophoblast stem cells. Nat Commun 5:3174

    Article  PubMed  Google Scholar 

  • Zhu Q, Huang Y, Marton LJ, Woster PM, Davidson NE, Casero RA Jr (2012) Polyamine analogs modulate gene expression by inhibiting lysine-specific demethylase 1 (LSD1) and altering chromatin structure in human breast cancer cells. Amino Acids 42:887–898

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Longevity and Aging Institute (LAI), IBS and Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, 200032, P.R. China

    Fei Mao & Yujiang Geno Shi

  2. Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Fei Mao & Yujiang Geno Shi

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  1. Fei Mao
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  2. Yujiang Geno Shi
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Correspondence to Yujiang Geno Shi .

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  1. Department of Pathology, Yale School of Medicine, New Haven, CT, USA

    Qin Yan

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Mao, F., Shi, Y.G. (2023). Targeting the LSD1/KDM1 Family of Lysine Demethylases in Cancer and Other Human Diseases. In: Yan, Q. (eds) Targeting Lysine Demethylases in Cancer and Other Human Diseases. Advances in Experimental Medicine and Biology, vol 1433. Springer, Cham. https://doi.org/10.1007/978-3-031-38176-8_2

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