PGC-1α regulates cell proliferation and invasion via AKT/GSK-3β/β-catenin pathway in human colorectal cancer SW620 and SW480 cells

Abstract

Background/Aim: Peroxisome proliferatoractivated receptor γ coactivator 1α (PGC-1α) is a master regulator of mitochondrial biogenesis and metabolism. We investigated the effect of PGC-1α knockdown in the human colorectal cancer cell line SW620, which highly expresses PGC-1α. Materials and Methods: We established the PGC- 1α shRNA-silenced SW620 stable cell line (PGC-1α shRNASW620 cells) and examined cell proliferation by cell counts and carboxyfluorescein succinimidyl ester (CFSE) staining, migration by wound-healing and transwell migration assay, and invasion by transwell assays. Results: PGC-1α knockdown inhibited cell proliferation, migration, and invasion in SW620 cells. Western blot analysis showed that p-AKT, p-GSK-3β, β-catenin, N-cadherin and vimentin expression were all reduced, but E-cadherin had increased expression in PGC-1α shRNA-SW620 cells. We also examined cell proliferation, migration, invasion and the expression of p-AKT, p-GSK-3β, β-catenin, N-cadherin, vimentin, and E-cadherin in PGC-1α overexpressing SW480 cells (a low PGC-1α expressing line). We observed a complete reversal of the results seen in the knockdown. Conclusion: PGC-1α might regulate cell proliferation and invasion via AKT/GSK-3β/β-catenin pathway in SW620 and SW480 cells.