Knockdown of FOXK1 suppresses liver cancer cell viability by inhibiting glycolysis

Aims: Aerobic glycolysis is a unique characteristic of cancer cells, and this key signature provides a target for therapeutic intervention of cancers. Forkhead box protein K1 (FOXK1) is a transcriptional factor that plays an oncogenic role in several types of cancers, including liver cancer. However, whether FOXK1 could affect glycolysis in cancer cells remains unknown. The aim of the present study was to evaluate the effect of FOXK1 on glycolysis in liver cancer cells. Main methods: The expression of FOXK1 in four human liver cancer cell lines was evaluated using qRT-PCR and western blot. Cell viability was assessed using MTT and CCK-8 assays. Glucose consumption and lactate production of the cells were detected to reflect glycolysis. The expression of hexokinase 2 (HK2) was detected using qRT-PCR and western blot. Key findings: FOXK1 was up-regulated in liver cancer cells as compared to the normal human hepatic cell line. Knockdown of FOXK1 reduced cell viability and HK2 expression. FOXK1 knockdown decreased glucose consumption and lactate production in liver cancer cells. Furthermore, FOXK1 knockdown suppressed the activation of Akt/mTOR pathway. Inhibition of Akt/mTOR pathway reduced cell viability and glycolysis of liver cancer cells. Significance: These findings suggested that FOXK1 knockdown inhibited cell viability of liver cancer cells by regulating glycolysis through the Akt/mTOR pathway.