Expression of fatty acid synthase is regulated by PGC‑1α and contributes to increased cell proliferation

We previously demonstrated that overexpression of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) promotes increased cell proliferation and tumorigenic potential through upregulation of specificity protein 1 (Sp1) and acyl-CoA-binding protein (ACBP). Fatty acid synthase (FASN) is a key enzyme in fatty acid biosynthesis, and its expression in various cancers is associated with survival, poor prognosis and cancer recurrence. In the present study, we evaluated whether PGC-1α regulated FASN expression in human colorectal cancer (SNU-C4 and HT-29) cells. We also examined whether cell proliferation was inhibited by shRNA‑induced FASN knockdown in SNU-C4 and HT-29 cells. In all tested cell lines, FASN-shRNA knockdown inhibited cell proliferation, decreased antioxidant enzyme expression, and increased apoptosis and production of H2O2‑induced reactive oxygen species (ROS). These findings indicated that FASN expression may enhance cell proliferation by regulating antioxidant enzyme production and resistance to ROS-induced apoptosis. We further provided evidence that FASN expression was regulated indirectly through upregulation of Sp1 and SREBP-1c by PGC-1α. Overall, our results revealed that FASN expression, mediated by PGC-1α, may play a positive role in cancer cell proliferation.