FOXK2 downregulation suppresses EMT in hepatocellular carcinoma

Forkhead box K2 (FOXK2), initially identified as an NFAT-like interleukin-binding factor, has been reported to function as either an oncogene or tumor suppressor depending on context. However, its role in regulating epithelial-mesenchymal transition (EMT) in hepatocellular carcinoma (HCC) remains poorly defined. In this study, FOXK2-specific siRNA was used to reduce endogenous FOXK2 expression in Hep3B and HCCLM3 cells. Cell proliferation, migration, and invasion were assessed using MTT, colony formation, and transwell assays, respectively. Protein levels related to EMT and the Akt signaling pathway were analyzed by western blotting.

FOXK2 knockdown significantly inhibited proliferation, colony formation, migration, and invasion in both HCC cell lines. This was accompanied by increased E-cadherin expression and reduced levels of Snail and phosphorylated Akt (p-Akt). Treatment with SF1670, an Akt pathway activator, reversed these effects—upregulating Snail and p-Akt, downregulating E-cadherin, and promoting invasion and colony formation. SF1670 partially counteracted the inhibitory effects of FOXK2 silencing, suggesting that FOXK2 regulates EMT in HCC in part through the Akt signaling pathway.

Conclusion: Downregulation of FOXK2 suppresses EMT and tumor progression in HCC cells, at least partly by inhibiting the Akt signaling pathway, highlighting FOXK2 as a potential therapeutic target in HCC.