Objective: To investigate the role of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) in the metastasis of colorectal cancer and underlying mechanisms.
Methods: A colorectal cancer LoVo cell line transfected with a lentivirus vector stably expressinga shRNA targeting PGC-1αwas established. Cell proliferation was detected by CCK8 array. Migration and invasion were determined by Transwell assay. The expressions of epithelial-mesenchymal transition (EMT) markers were examined by western blot analysis.
Results: Down-regulation of PGC-1α significantly inhibited the migration (74.4±4.5 versus 31.4±3.8,P<0.05), invasion (55.0±7.7 versus 17.6±5.0,P<0.05) and anoikis resistance (32.3±4.3)% versus (54.3±4.8)%,P<0.05, of LoVo cells. However, knockdown of PGC-1α had little effect on cell proliferation. Moreover, knockdown of PGC-1α induced EMT of LoVo cells by up-regulating E-cadherin and down-regulating vimentin. Alternatively, the expression of PGC-1α was induced by cell detachment. PGC-1αexpression was also higher in the colorectal cancer tissues than that in para-cancerous tissues, and its expression in the invading front area was higher than that in the tumor center area.
Conclusion: PGC-1α plays an important role in the metastasis of colorectal cancer, which may promote the invasion and anoikis resistance of colorectal cancer cells through EMT induction.