Targeting PGC1α to wrestle cancer: a compelling therapeutic opportunity

Metabolic adaptation is an emerging hallmark of cancer, as it provides tumor cells sufficient energy and metabolic intermediates. Although tumor cells are believed to highly rely on Warburg effect to satisfy their energy demand, more studies have pointed out that various types of tumor cells are highly dependent on oxidative phosphorylation to drive the tumorigenesis. Peroxisome proliferator-activated receptor-c coactivator 1α (PGC1α), the crucial member of PGC1 family, is aberrantly expressed in several cancer types, implicating its role in tumor proliferation, migration, invasion, metastasis, and chemoresistance. Numerous studies have reported that PGC1α participates in the regulation of tumor development by altering the transcriptional programs as well as the metabolic phenotypes. Thus, PGC1α-targeted therapy is therapeutically exploitable to target the metabolic vulnerabilities in tumor cells. This review mainly focuses on the current underlying mechanisms for its roles in regulating metabolic adaptation of tumor cells and its upstream regulators; how PGC1α participates in the regulation of the tumor proliferation, migration, invasion, metastasis, therapy resistance; and the feasibility of PGC1α-targeted therapy for cancer treatment.