Original ResearchFull Report: Basic and Translational—Alimentary TractFOXM1-Induced PRX3 Regulates Stemness and Survival of Colon Cancer Cells via Maintenance of Mitochondrial Function
Section snippets
Materials and Methods
Detailed Materials and Methods are available in the Supplementary Material.
Colon Cancer Stem Cells Utilize Primary Mitochondrial Oxidative Phosphorylation Rather Than Glycolysis to Produce Adenosine Triphosphate
We assessed potential differences in mitochondrial function between colon CSCs and non-CSCs using antibody-based detection of CD133, CD44, and Lgr5 (Figure 1). The CD133+CD44+Lgr5+ cells (CSCs) had a higher mitochondrial membrane potential (ΔΨm), and increased levels of Ca2+ and ROS compared with CD133−CD44−Lgr5- cells (non-CSCs) (Figure 1A−C). In addition, the oxygen consumption rates and mitochondrial ATP levels of CSCs were much higher than non-CSCs, and lactate production was higher in
Discussion
In the current study, we found that highly expressed mitochondrial Prx3 plays a critical role in maintaining mitochondrial function via elimination of ROS produced by ATP production in the OXPHOS system in CSCs. This role of Prx3 is important for promoting stemness and survival of CSCs. We further showed that Prx3 and CD133 expression is up-regulated by the transcription factor FoxM1 in colon CSCs. We also showed that the mitochondrial function of colon CSCs is improved in comparison with that
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2021, Redox BiologyCitation Excerpt :However, we have recently demonstrated that colon CSCs utilize the mitochondrial oxidative phosphorylation (OXPHOS) system to generate ATP and increase reactive oxygen species (ROS) levels when compared to non-CSCs. Moreover, colon CSCs potentially utilize primary OXPHOS rather than glycolysis to produce ATP [6]. Notably, colon CSCs exhibit increased mitochondrial function compared to colon bulk tumor cells [7,8].
Conflicts of interest The authors disclose no conflicts.
Funding This study was supported by a grant from a Priority Research Centers Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science, and Technology (2010-0020224), and a Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science, and Technology (2012R1A1A2041700 and 2012R1A2A1A03007595).
Author names in bold designate shared co-first authorship.