Hypoxia-induced PGC-1 alpha Regulates Mitochondrial Function and Tumorigenesis of Colorectal Cancer Cells

Abstract

Background/Aim: Hypoxia promotes tumor proliferation and metastasis in colorectal cancer (CRC). Since the tumor microenvironment is generally characterized by hypoxia, its understanding is important for cancer therapy. We hypothesized that hypoxia promotes the mitochondrial function, mobility, and proliferation of CRC by up-regulating peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1 alpha). Materials and Methods: To assess the effects of PGC-1 alpha under hypoxia, we investigated the mitochondrial function, cell motility, and sphere formation as well as proliferation and apoptosis of CRC. Results: Under hypoxia, we confirmed the increased expression of PGC-1 alpha and reduced production of reactive oxygen species (ROS) by activating anti-oxidant enzymes. Also, up-regulation of PGC-1 alpha enhanced the motility, sphere formation, and proliferation of CRC. Under the presence of the anti-cancer drug 5-fluorouracil (5FU), up-regulation of PGC-1 alpha under hypoxia promoted resistance of CRC against 5FU-induced apoptosis. Conclusion: Targeting PGC-1 alpha could to be a powerful strategy for CRC therapy.