The metabolic modulator PGC-1α in cancer

Abstract

The peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) is a central modulator of cell metabolism. It regulates mitochondrial biogenesis and oxidative metabolism. Modifications and adaptations in cellular metabolism are hallmarks of cancer cells, thus, it is not surprising that PGC-1α plays a role in cancer. Several recent articles have shown that PGC-1α expression is altered in tumors and metastasis in relation to modifications in cellular metabolism. The potential uses of PGC-1α as a therapeutic target and a biomarker of the advanced form of cancer will be summarized in this review.

Keywords: PGC1 alpha; breast cancer; melanoma; metabolism; mitochondria; pancreatic cancer; prostate cancer.

Figure 1

The PGC-1 protein family members. Schematic representation of the three members of the PGC-1 family, indicating their different regions and the % of homology between each member in the N and C-terminal region of the co-activators.

Figure 2

PGC-1α, a co-activator implicated in several biological functions. PGC-1α gene expression is mainly regulated by three transcription factors (CREB, ATF2 and MEF2) that bind to the CREB-responsive element (CRE) and myocyte enhancer factor-2 (MEF2). The protein is also regulated by post-translational modifications such as phosphorylation, deacetylation, acetylation and methylation. PGC-1α interacts with numerous transcription factors and is implicated in several biological functions.

Figure 3

PGC-1α and cancer. Schematic summary of the different roles of PGC-1α in melanoma, breast, prostate and pancreatic cancer. The expression of PGC-1α is associated with modifications to cancer cell metabolism, different phenotypes associated with the aggressiveness of the cancer and patient survival.