Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

The protein tyrosine phosphatase DEP-1/PTPRJ promotes breast cancer cell invasion and metastasis

Abstract

DEP-1/PTPRJ is a receptor-like protein tyrosine phosphatase mainly known for its antiproliferative and tumor-suppressive functions. Many identified substrates are growth factor receptors, and DEP-1 is deleted and/or mutated in human cancers including that of the breast. However, DEP-1 was also identified as a promoter of Src activation and proinvasive functions in the endothelium, suggesting it could perhaps mediate breast cancer invasiveness that is likewise driven by Src family kinases. We show here that DEP-1 expression was greater in highly invasive breast cancer cells (MDA-MB-231, Hs578T, BT-549) than in the less invasive or untransformed cell lines tested (MCF-7, T47D, SK-BR3 and MCF10A). DEP-1 silencing experiments in invasive cells demonstrated that moderately expressed and catalytically active DEP-1 was required, in collaboration with basal epidermal growth factor receptor activity, for Src activation and the phosphorylation of its substrate Cortactin, and for their colocalization at the cell’s leading edge. This correlated with an increased number of cell protrusions, and an enhanced capacity of the cells to migrate and invade. Similarly, moderate overexpression of DEP-1 in the low-invasive cells resulted in the promotion of their invasiveness in an Src-dependent manner. Consistent with these data, the expression of endogenous DEP-1 was elevated in a bone metastatic cell line derived from MDA-MB-231 cells, and promoted increased Src Y418 and Cortactin Y421 phosphorylation, as well as pro-MMP9 secretion and Matrigel invasion. Importantly, the silencing of DEP-1 in MDA-MB-231 cells greatly decreased their ability to metastasize, despite having no effect on tumor growth or angiogenesis. Hence, we found that moderate expression of DEP-1 was associated with the increased relapse and decreased survival of breast cancer patients. These results therefore identify a new and unsuspected role for DEP-1 as a mediator of an invasive cell program implicating Src activation and the promotion of breast cancer progression.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7

Similar content being viewed by others

References

  1. Östman A, Hellberg C, Böhmer FD . Protein-tyrosine phosphatases and cancer. Nat Rev Cancer 2006; 6: 307–320.

    Article  PubMed  Google Scholar 

  2. Tonks NK . Protein tyrosine phosphatases—from housekeeping enzymes to master regulators of signal transduction. FEBS J 2013; 280: 346–378.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Julien SG, Dube N, Hardy S, Tremblay ML . Inside the human cancer tyrosine phosphatome. Nat Rev Cancer 2011; 11: 35–49.

    Article  CAS  PubMed  Google Scholar 

  4. Ruivenkamp C, Hermsen M, Postma C, Klous A, Baak J, Meijer G et al. LOH of PTPRJ occurs early in colorectal cancer and is associated with chromosomal loss of 18q12-21. Oncogene 2003; 22: 3472–3474.

    Article  CAS  PubMed  Google Scholar 

  5. Iuliano R, Le Pera I, Cristofaro C, Baudi F, Arturi F, Pallante P et al. The tyrosine phosphatase PTPRJ/DEP-1 genotype affects thyroid carcinogenesis. Oncogene 2004; 23: 8432–8438.

    Article  CAS  PubMed  Google Scholar 

  6. Petermann A, Haase D, Wetzel A, Balavenkatraman KK, Tenev T, Guhrs KH et al. Loss of the protein-tyrosine phosphatase DEP-1/PTPRJ drives meningioma cell motility. Brain Pathol 2011; 21: 405–418.

    Article  CAS  PubMed  Google Scholar 

  7. Aya-Bonilla C, Green MR, Camilleri E, Benton M, Keane C, Marlton P et al. High-resolution loss of heterozygosity screening implicates PTPRJ as a potential tumor suppressor gene that affects susceptibility to non-Hodgkin's lymphoma. Genes Chromosomes Cancer 2013; 52: 467–479.

    Article  CAS  PubMed  Google Scholar 

  8. Smart CE, Askarian Amiri ME, Wronski A, Dinger ME, Crawford J, Ovchinnikov DA et al. Expression and function of the protein tyrosine phosphatase receptor J (PTPRJ) in normal mammary epithelial cells and breast tumors. PLoS One 2012; 7: e40742.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Mita Y, Yasuda Y, Sakai A, Yamamoto H, Toyooka S, Gunduz M et al. Missense polymorphisms of PTPRJ and PTPN13 genes affect susceptibility to a variety of human cancers. J Cancer Res Clin Oncol 2010; 136: 249–259.

    Article  CAS  PubMed  Google Scholar 

  10. Iuliano R, Palmieri D, He H, Iervolino A, Borbone E, Pallante P et al. Role of PTPRJ genotype in papillary thyroid carcinoma risk. Endocr Relat Cancer 2010; 17: 1001–1006.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Ellinghaus E, Stanulla M, Richter G, Ellinghaus D, te Kronnie G, Cario G et al. Identification of germline susceptibility loci in ETV6-RUNX1-rearranged childhood acute lymphoblastic leukemia. Leukemia 2012; 26: 902–909.

    Article  CAS  PubMed  Google Scholar 

  12. Lesueur F, Pharoah PD, Laing S, Ahmed S, Jordan C, Smith PL et al. Allelic association of the human homologue of the mouse modifier Ptprj with breast cancer. Hum Mol Genet 2005; 14: 2349–2356.

    Article  CAS  PubMed  Google Scholar 

  13. Lampugnani MG, Zanetti A, Corada M, Takahashi T, Balconi G, Breviario F et al. Contact inhibition of VEGF-induced proliferation requires vascular endothelial cadherin, β-catenin, and the phosphatase DEP-1/CD148. J Cell Biol 2003; 161: 793–804.

    Article  CAS  PubMed Central  Google Scholar 

  14. Keane M, Lowrey G, Ettenberg S, Dayton M, Lipkowitz S . The protein tyrosine phosphatase DEP-1 is induced during differentiation and inhibits growth of breast cancer cells. Cancer Res 1996; 56: 4236–4243.

    CAS  PubMed  Google Scholar 

  15. Balavenkatraman KK, Jandt E, Friedrich K, Kautenburger T, Pool-Zobel BL, Ostman A et al. DEP-1 protein tyrosine phosphatase inhibits proliferation and migration of colon carcinoma cells and is upregulated by protective nutrients. Oncogene 2006; 25: 6319–6324.

    Article  CAS  PubMed  Google Scholar 

  16. Zhang L, Martelli ML, Battaglia C, Trapasso F, Tramontano D, Viglietto G et al. Thyroid cell transformation inhibits the expression of a novel rat protein tyrosine phosphatase. Exp Cell Res 1997; 235: 62–70.

    Article  CAS  PubMed  Google Scholar 

  17. Trapasso F, Iuliano R, Boccia A, Stella A, Visconti R, Bruni P et al. Rat protein tyrosine phosphatase eta suppresses the neoplastic phenotype of retrovirally transformed thyroid cells through the stabilization of p27Kip1. Mol Cell Biol 2000; 20: 9236–9246.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Trapasso F, Yendamuri S, Dumon KR, Iuliano R, Cesari R, Feig B et al. Restoration of receptor-type protein tyrosine phosphatase {eta} function inhibits human pancreatic carcinoma cell growth in vitro and in vivo. Carcinogenesis 2004; 25: 2107–2114.

    Article  CAS  PubMed  Google Scholar 

  19. Takahashi T, Takahashi K, Mernaugh R, Drozdoff V, Sipe C, Schoecklmann H et al. Endothelial localization of receptor tyrosine phosphatase, ECRTP/DEP-1, in developing and mature renal vasculature. J Am Soc Nephrol 1999; 10: 2135–2145.

    CAS  PubMed  Google Scholar 

  20. Sallee JL, Burridge K . Density-enhanced phosphatase 1 regulates phosphorylation of tight junction proteins and enhances barrier function of epithelial cells. J Biol Chem 2009; 284: 14997–15006.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Holsinger LJ, Ward K, Duffield B, Zachwieja J, Jallal B . The transmembrane receptor protein tyrosine phosphatase DEP1 interacts with p120ctn. Oncogene 2002; 21: 7067–7076.

    Article  CAS  PubMed  Google Scholar 

  22. Palka HL, Park M, Tonks NK . Hepatocyte growth factor receptor tyrosine kinase Met is a substrate of the receptor protein-tyrosine phosphatase DEP-1. J Biol Chem 2003; 278: 5728–5735.

    Article  CAS  PubMed  Google Scholar 

  23. Kovalenko M, Denner K, Sandstrom J, Persson C, Gross S, Jandt E et al. Site-selective dephosphorylation of the platelet-derived growth factor beta-receptor by the receptor-like protein-tyrosine phosphatase DEP-1. J Biol Chem 2000; 275: 16219–16226.

    Article  CAS  PubMed  Google Scholar 

  24. Chabot C, Spring K, Gratton JP, Elchebly M, Royal I . New role for the protein tyrosine phosphatase DEP-1 in Akt activation and endothelial cell survival. Mol Cell Biol 2009; 29: 241–253.

    Article  CAS  PubMed  Google Scholar 

  25. Berset TA, Hoier EF, Hajnal A . The C. elegans homolog of the mammalian tumor suppressor Dep-1/Scc1 inhibits EGFR signaling to regulate binary cell fate decisions. Genes Dev 2005; 19: 1328–1340.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Tarcic G, Boguslavsky SK, Wakim J, Kiuchi T, Liu A, Reinitz F et al. An unbiased screen identifies DEP-1 tumor suppressor as a phosphatase controlling EGFR endocytosis. Curr Biol 2009; 19: 1788–1798.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Arora D, Stopp S, Bohmer SA, Schons J, Godfrey R, Masson K et al. Protein-tyrosine phosphatase DEP-1 controls receptor tyrosine kinase FLT3 signaling. J Biol Chem 2011; 286: 10918–10929.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Zhu JW, Brdicka T, Katsumoto TR, Lin J, Weiss A . Structurally distinct phosphatases CD45 and CD148 both regulate B cell and macrophage immunoreceptor signaling. Immunity 2008; 28: 183–196.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Senis YA, Tomlinson MG, Ellison S, Mazharian A, Lim J, Zhao Y et al. The tyrosine phosphatase CD148 is an essential positive regulator of platelet activation and thrombosis. Blood 2009; 113: 4942–4954.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Le Pera I, Iuliano R, Florio T, Susini C, Trapasso F, Santoro M et al. The rat tyrosine phosphatase eta increases cell adhesion by activating c-Src through dephosphorylation of its inhibitory phosphotyrosine residue. Oncogene 2005; 24: 3187–3195.

    Article  CAS  Google Scholar 

  31. Spring K, Chabot C, Langlois S, Lapointe L, Trinh NTN, Caron C et al. Tyrosine phosphorylation of DEP-1/CD148 as a mechanism controlling Src kinase activation, endothelial cell permeability, invasion, and capillary formation. Blood 2012; 120: 2745–2756.

    Article  CAS  PubMed  Google Scholar 

  32. Ishizawar R, Parsons SJ . c-Src and cooperating partners in human cancer. Cancer Cell 2004; 6: 209–214.

    Article  CAS  PubMed  Google Scholar 

  33. Frame MC . Src in cancer: deregulation and consequences for cell behaviour. Biochim Biophys Acta 2002; 1602: 114–130.

    CAS  PubMed  Google Scholar 

  34. Kim LC, Song L, Haura EB . Src kinases as therapeutic targets for cancer. Nat Rev Clin Oncol 2009; 6: 587–595.

    Article  PubMed  Google Scholar 

  35. Shor AC, Keschman EA, Lee FY, Muro-Cacho C, Letson GD, Trent JC et al. Dasatinib inhibits migration and invasion in diverse human sarcoma cell lines and induces apoptosis in bone sarcoma cells dependent on SRC kinase for survival. Cancer Res 2007; 67: 2800–2808.

    Article  CAS  PubMed  Google Scholar 

  36. Zhang S, Yu D . Targeting Src family kinases in anti-cancer therapies: turning promise into triumph. Trends Pharmacol Sci 2012; 33: 122–128.

    Article  PubMed  Google Scholar 

  37. Zhang XHF, Wang Q, Gerald W, Hudis CA, Norton L, Smid M et al. Latent bone metastasis in breast cancer tied to Src-dependent survival signals. Cancer Cell 2009; 16: 67–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Rucci N, Recchia I, Angelucci A, Alamanou M, Del Fattore A, Fortunati D et al. Inhibition of protein kinase c-Src reduces the incidence of breast cancer metastases and increases survival in mice: implications for therapy. J Pharmacol Exp Ther 2006; 318: 161–172.

    Article  CAS  PubMed  Google Scholar 

  39. Myoui A, Nishimura R, Williams PJ, Hiraga T, Tamura D, Michigami T et al. C-SRC tyrosine kinase activity is associated with tumor colonization in bone and lung in an animal model of human breast cancer metastasis. Cancer Res 2003; 63: 5028–5033.

    CAS  PubMed  Google Scholar 

  40. Verbeek BS, Vroom TM, Adriaansen-Slot SS, Ottenhoff-Kalff AE, Geertzema JGN, Hennipman A et al. c-Src protein expression is increased in human breast cancer. An immunohistochemical and biochemical analysis. J Pathol 1996; 180: 383–388.

    Article  CAS  PubMed  Google Scholar 

  41. Nam JS, Ino Y, Sakamoto M, Hirohashi S . Src family kinase inhibitor PP2 restores the E-cadherin/catenin cell adhesion system in human cancer cells and reduces cancer metastasis. Clin Cancer Res 2002; 8: 2430–2436.

    CAS  PubMed  Google Scholar 

  42. Hochgräfe F, Zhang L, O'Toole SA, Browne BC, Pinese M, Porta Cubas A et al. Tyrosine phosphorylation profiling reveals the signaling network characteristics of basal breast cancer cells. Cancer Res 2010; 70: 9391–9401.

    Article  PubMed  Google Scholar 

  43. Smid M, Wang Y, Zhang Y, Sieuwerts AM, Yu J, Klijn JGM et al. Subtypes of breast cancer show preferential site of relapse. Cancer Res 2008; 68: 3108–3114.

    Article  CAS  PubMed  Google Scholar 

  44. Sihto H, Lundin J, Lundin M, Lehtimaki T, Ristimaki A, Holli K et al. Breast cancer biological subtypes and protein expression predict for the preferential distant metastasis sites: a nationwide cohort study. Breast Cancer Res 2011; 13: R87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Bertos NR, Park M . Breast cancer—one term, many entities? J Clin Invest 2011; 121: 3789–3796.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Podo F, Buydens LMC, Degani H, Hilhorst R, Klipp E, Gribbestad IS et al. Triple-negative breast cancer: present challenges and new perspectives. Mol Oncol 2010; 4: 209–229.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Lehmann BD, Bauer JA, Chen X, Sanders ME, Chakravarthy AB, Shyr Y et al. Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest 2011; 121: 2750–2767.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Hiscox S, Morgan L, Green T, Barrow D, Gee J, Nicholson RI . Elevated Src activity promotes cellular invasion and motility in tamoxifen resistant breast cancer cells. Breast Cancer Res Treat 2006; 97: 263–274.

    Article  CAS  PubMed  Google Scholar 

  49. Elias D, Vever H, Lankholm AV, Gjerstorff MF, Yde CW, Lykkesfeldt AE et al. Gene expression profiling identifies FYN as an important molecule in tamoxifen resistance and a predictor of early recurrence in patients treated with endocrine therapy. Oncogene 2014. 1–9.

  50. Eccles SA . The epidermal growth factor receptor/Erb-B/HER family in normal and malignant breast biology. Int J Dev Biol 2011; 55: 685–696.

    Article  PubMed  Google Scholar 

  51. Foley J, Nickerson NK, Nam S, Allen KT, Gilmore JL, Nephew KP et al. EGFR signaling in breast cancer: bad to the bone. Semin Cell Dev Biol 2010; 21: 951–960.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Chiorean R, Braicu C, Berindan-Neagoe I . Another review on triple negative breast cancer. Are we on the right way towards the exit from the labyrinth? Breast 2013; 22: 1026–1033.

    Article  PubMed  Google Scholar 

  53. Taube JH, Herschkowitz JI, Komurov K, Zhou AY, Gupta S, Yang J et al. Core epithelial-to-mesenchymal transition interactome gene-expression signature is associated with claudin-low and metaplastic breast cancer subtypes. Proc Natl Acad Sci USA 2010; 107: 15449–15454.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Spring K, Lapointe L, Caron C, Langlois S, Royal I . Phosphorylation of DEP-1/PTPRJ on Threonine 1318 regulates its ability to promote Src activation and endothelial cell permeability. Cell Signal 2014; 26: 1283–1293.

    Article  CAS  PubMed  Google Scholar 

  55. Rhodes DR, Yu J, Shanker K, Deshpande N, Varambally R, Ghosh D et al. ONCOMINE: A Cancer Microarray Database and Integrated Data-Mining Platform. Neoplasia 2004; 6: 1–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. MacGrath SM, Koleske AJ . Cortactin in cell migration and cancer at a glance. J Cell Sci 2012; 125: 1621–1626.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Li Y, Tondravi M, Liu J, Smith E, Haudenschild CC, Kaczmarek M et al. Cortactin potentiates bone metastasis of breast cancer cells. Cancer Res 2001; 61: 6906–6911.

    CAS  PubMed  Google Scholar 

  58. Clark ES, Weaver AM . A new role for cortactin in invadopodia: regulation of protease secretion. Eur J Cell Biol 2008; 87: 581–590.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Bryce NS, Clark ES, Leysath JL, Currie JD, Webb DJ, Weaver AM . Cortactin promotes cell motility by enhancing lamellipodial persistence. Curr Biol 2005; 15: 1276–1285.

    Article  CAS  PubMed  Google Scholar 

  60. Tehrani S, Tomasevic N, Weed S, Sakowicz R, Cooper JA . Src phosphorylation of cortactin enhances actin assembly. Proc Natl Acad Sci USA 2007; 104: 11933–11938.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Sung Bong H, Zhu X, Kaverina I, Weaver Alissa M . Cortactin controls cell motility and lamellipodial dynamics by regulating ECM secretion. Curr Biol 2011; 21: 1460–1469.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Mezi S, Todi L, Orsi E, Angeloni A, Mancini P . Involvement of the Src-cortactin pathway in migration induced by IGF-1 and EGF in human breast cancer cells. Int J Oncol 2012; 41: 2128–2138.

    Article  CAS  PubMed  Google Scholar 

  63. Guarino M . Src signaling in cancer invasion. J Cell Physiol 2010; 223: 14–26.

    CAS  PubMed  Google Scholar 

  64. Jallal H, Valentino M-L, Chen G, Boschelli F, Ali S, Rabbani SA . A Src/Abl kinase inhibitor, SKI-606, blocks breast cancer invasion, growth, and metastasis in vitro and in vivo. Cancer Res 2007; 67: 1580–1588.

    Article  CAS  PubMed  Google Scholar 

  65. Ma J-G, Huang H, Chen S-m, Chen Y, Xin X-l, Lin L-p et al. PH006, a novel and selective Src kinase inhibitor, suppresses human breast cancer growth and metastasis in vitro and in vivo. Breast Cancer Res Treat 2011; 130: 85–96.

    Article  CAS  PubMed  Google Scholar 

  66. Shields BJ, Wiede F, Gurzov EN, Wee K, Hauser C, Zhu H-J et al. TCPTP regulates SFK and STAT3 signaling and is lost in triple-negative breast cancers. Mol Cell Biol 2013; 33: 557–570.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Aceto N, Sausgruber N, Brinkhaus H, Gaidatzis D, Martiny-Baron G, Mazzarol G et al. Tyrosine phosphatase SHP2 promotes breast cancer progression and maintains tumor-initiating cells via activation of key transcription factors and a positive feedback signaling loop. Nat Med 2012; 18: 529–537.

    Article  CAS  PubMed  Google Scholar 

  68. Bentires-Alj M, Neel BG . Protein-tyrosine phosphatase 1B is required for HER2/Neu-induced breast cancer. Cancer Res 2007; 67: 2420–2424.

    Article  CAS  PubMed  Google Scholar 

  69. Julien SG, Dube N, Read M, Penney J, Paquet M, Han Y et al. Protein tyrosine phosphatase 1B deficiency or inhibition delays ErbB2-induced mammary tumorigenesis and protects from lung metastasis. Nat Genet 2007; 39: 338–346.

    Article  CAS  PubMed  Google Scholar 

  70. Sun T, Aceto N, Meerbrey Kristen L, Kessler Jessica D, Zhou C, Migliaccio I et al. Activation of multiple proto-oncogenic tyrosine kinases in breast cancer via loss of the PTPN12 phosphatase. Cell 2011; 144: 703–718.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Hardy S, Wong NN, Muller WJ, Park M, Tremblay ML . Overexpression of the protein tyrosine phosphatase PRL-2 correlates with breast tumor formation and progression. Cancer Res 2010; 70: 8959–8967.

    Article  CAS  PubMed  Google Scholar 

  72. Yu M, Lin G, Arshadi N, Kalatskaya I, Xue B, Haider S et al. Expression profiling during mammary epithelial cell three-dimensional morphogenesis identifies PTPRO as a novel regulator of morphogenesis and ErbB2-mediated transformation. Mol Cell Biol 2012; 32: 3913–3924.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Sabe H, Hashimoto S, Morishige M, Hashimoto A, Ogawa E . The EGFR-GEP100-Arf6 pathway in breast cancer: full invasiveness is not from the inside. Cell Adhes Migr 2008; 2: 71–73.

    Article  Google Scholar 

  74. Clark ES, Whigham AS, Yarbrough WG, Weaver AM . Cortactin is an essential regulator of matrix metalloproteinase secretion and extracellular matrix degradation in invadopodia. Cancer Res 2007; 67: 4227–4235.

    Article  CAS  PubMed  Google Scholar 

  75. Lai FP, Szczodrak M, Oelkers JM, Ladwein M, Acconcia F, Benesch S et al. Cortactin promotes migration and platelet-derived growth factor-induced actin reorganization by signaling to Rho-GTPases. Mol Biol Cell 2009; 20: 3209–3223.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Majumder S, Sowden MP, Gerber SA, Thomas T, Christie CK, Mohan A et al. G-protein–coupled receptor-2–interacting protein-1 is required for endothelial cell directional migration and tumor angiogenesis via cortactin-dependent lamellipodia formation. Arterioscler Thromb Vasc Biol 2014; 34: 419–426.

    Article  CAS  PubMed  Google Scholar 

  77. Takahashi K, Suzuki K . Density-dependent inhibition of growth involves prevention of EGF receptor activation by E-cadherin-mediated cell–cell adhesion. Exp Cell Res 1996; 226: 214–222.

    Article  CAS  PubMed  Google Scholar 

  78. Eckert LB, Repasky GA, Ülkü AS, McFall A, Zhou H, Sartor CI et al. Involvement of Ras activation in human breast cancer cell signaling, invasion, and anoikis. Cancer Res 2004; 64: 4585–4592.

    Article  CAS  PubMed  Google Scholar 

  79. Ding L, Ellis MJ, Li S, Larson DE, Chen K, Wallis JW et al. Genome remodelling in a basal-like breast cancer metastasis and xenograft. Nature 2010; 464: 999–1005.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank our colleagues for their generous gifts of plasmid DNAs and cell lines. This work was supported by a Cancer Research Society/Quebec Breast Cancer Foundation grant (to IR). KS and CC held partial studentships from Université de Montréal. PF was supported by FRQS (25988) and CIHR (292353) studentships. KS, PF, CC and JR also held partial studentships from the Montreal Cancer Institute.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to I Royal.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Additional information

Supplementary Information accompanies this paper on the Oncogene website

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Spring, K., Fournier, P., Lapointe, L. et al. The protein tyrosine phosphatase DEP-1/PTPRJ promotes breast cancer cell invasion and metastasis. Oncogene 34, 5536–5547 (2015). https://doi.org/10.1038/onc.2015.9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/onc.2015.9

This article is cited by

Search

Quick links