Peroxisome Proliferator-Activated Receptor γ and PGC-1α in Cancer: Dual Actions as Tumor Promoter and Suppressor

Table 2

The role and action mechanisms of PGC-1 in cancer.

Experimental system		Role and action mechanisms	References
Modification	Cell type
Tumor-promoting functions of PGC-1
PGC-1 knockdown	Human prostate cancer PC3, LNCap cells	Stimulation of cell proliferation; activation of androgen receptor	[17]
Increased PGC-1 expression in arsenic-induced skin cancer	Skin cancer	Stimulation of cell proliferation; enhanced mitochondrial biogenesis	[34]
Pgc-1 knockout and knockdown by lentivirus-based PGC-1 shRNA	Human colorectal cancer cell line (Colo205)	Stimulation of carcinogenesis and tumor growth; induction of lipogenic enzymes	[35]
PGC-1 overexpression by PGC-1 plasmid	Human embryonic kidney cells, human colorectal cancer SNU-C4 cells, xenograft model	Stimulation of cell proliferation and tumorigenesis; upregulation of Sp1 and ACBP; upregulation of antioxidant enzyme (catalase, SOD)	[36]
PGC-1 shRNA knockdown	Human melanoma PGC-1-positive A375 cells, xenograft model	Inhibition of apoptosis; decreased ROS production, induction of ROS detoxifying enzymes	[37]
Increased PGC-1 expression in breast cancer cell	Breast cancer cell	Stimulation of cell proliferation; enhanced glutamine-mediated lipid biosynthesis	[38]
Pgc-1 shRNA knockdown	Human prostate cancer cell line (C4-2 cells)	Stimulation of cell proliferation; increased mitochondrial biogenesis	[39]
PGC-1 shRNA knockdown and PGC-1 overexpression	Human breast cancer cell, human melanoma cells	Stimulation of cell proliferation, increased invasion; increased mitochondrial biogenesis and oxidative phosphorylation	[40]
Anticancer functions of PGC-1
PGC-1 overexpression by adenovirus infection	Human ovarian cancer cell line (Ho-8910)	Induction of apoptosis; downregulation of Bcl-2 and upregulation of Bax	[41]
PGC-1 overexpression by adenovirus infection	Human hepatoma cell line (HepG2)	Inhibition of cell motility; upregulation of E-cadherin	[42]
PGC-1 overexpression	Human colorectal cancer cell lines (HT29 and HCT116)	Induction of apoptosis; ROS accumulation	[43]
Increased expression of PGC-1 by bezafibrate (PPAR panagonist)	Human cancer cell lines (HeLa, 143B, MDA-MB-231)	Inhibition of cell proliferation and invasion; increased mitochondrial biogenesis	[44]
PGC-1 overexpression	Human prostate cancer cell	Inhibition of cell proliferation and inhibition of metastasis; activation of ERR-dependent transcriptional program; induction of catabolic state	[45]
PGC-1 overexpression by adenovirus infection, CRISPR-mediated PGC-1 depletion	Human melanoma cell	Inhibition of metastasis; inhibition of inhibitor of DNA binding protein 2 (ID2) and TCF-mediated gene transcription	[46]