Peroxisome-proliferator activated receptor gamma coactivator-1 alpha (PGC-1α) upregulated E-cadherin expression in hepatoma cells

Peroxisome-proliferator activated receptor gamma coactivator-1 alpha (PGC-1α) is a highly inducible transcription factor coactivator that regulates biological programs linked to energy homeostasis and overexpression of PGC-1α could enhance mitochondrial biogenesis and functions. In a previous study, we have reported that PGC-1α expression was significantly repressed in hepatocellular carcinoma (HCC), which matches with the observation that one of the frequent metabolic alterations in most cancer cells is the conversion from oxidative to more glycolytic metabolism. In order to assess the role of PGC-1α in HCC progression in more details, we examined the effect of an adenoviral-mediated overexpression of human PGC-1α in HepG2 cells. After virus introduced into HepG2 cells, we found that the PGC-1αoverexpressing cells exhibited more round and condense pattern in comparison with the GFP transfected control cells. Consequently, we examined whether the expression of E-cadherin, an adherence junction protein whose expression is frequently reduced in various malignant tissues is altered in these cells. RT-PCR and Western blot analyses revealed that both mRNA and protein levels of E-cadherin were dramatically upregulated in PGC-1α-overexpressing cells. Immunofluorescence staining showed that E-cadherin accumulated to the cell membrane, where it forms functional adherence-junctions. In addiction, we found that expression of reporter gene driven by the E-cadherin promoter was up-regulated by PGC-1α . In addiction, real-time RT-PCR analysis of the expression of PGC-1α and E-cadherin genes in human HCCs tissue (n=16) were significantly reduced compared with surrounding non-tumorous liver tissue, and the downregulation of these two genes was highly correlated. Together, these results suggest that PGC-1α plays an important role in up-regulating E-cadherin expression in hepatoma cells and the correlation of PGC-1α and E-cadherin downregulation maybe involved in HCC progression.