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Anticancer Res. 2019 Sep;39(9):4865-4876. doi: 10.21873/anticanres.13672.

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

Yun CW1, Lee JH1,2, Lee SH3,2.

Author information

1
Medical Science Research Institute, Soonchunhyang University Seoul Hospital, Seoul, Republic of Korea.
2
Departments of Biochemistry, Soonchunhyang University College of Medicine, Cheonan, Republic of Korea.
3
Medical Science Research Institute, Soonchunhyang University Seoul Hospital, Seoul, Republic of Korea ykckss1114@nate.com jhlee0407@sch.ac.kr.

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-1α).

MATERIALS AND METHODS:

To assess the effects of PGC-1α 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-1α and reduced production of reactive oxygen species (ROS) by activating anti-oxidant enzymes. Also, up-regulation of PGC-1α enhanced the motility, sphere formation, and proliferation of CRC. Under the presence of the anti-cancer drug 5-fluorouracil (5FU), up-regulation of PGC-1α under hypoxia promoted resistance of CRC against 5FU-induced apoptosis.

CONCLUSION:

Targeting PGC-1α could to be a powerful strategy for CRC therapy.

KEYWORDS:

Colorectal cancer; PGC-1α; apoptosis; hypoxia; mitochondrial biogenesis; proliferation

PMID:
31519589
DOI:
10.21873/anticanres.13672
[Indexed for MEDLINE]

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