The role of hexokinase 2 in the metastasis of hepatocellular carcinoma cells

Abstract Objective: To investigate the regulatory role of HK2 in the metastasis of hepatocellular carcinoma (HCC). Methods: The protein expressions of HK2 in 73 HCC tumor tissues and paired adjacent non-tumor tissues were evaluated by using immunohistochemical analysis. The scratch wound healing assay and Transwell assay had been used to analyze the migration and invasion of HCC cells with HK2 knockdown. Expressions of epithelial-to-mesenchymal transition (EMT)markers, such as E-cadherin, ZO-1, N-cadherin and vimentin, in HCC cells with HK2 knockdown were determined by qRT-PCR and Western blot analysis. Results: The expression levels of HK2 in tumor tissues and adjacent non-tumor tissues were 5.39±3.40 and 2.16±1.55, respectively. The protein expression of HK2 was significantly higher in tumor tissues compared with adjacent non-tumor tissues of HCC (P<0.05). Knockdown of HK2 in HCC cells decreased the cell motility from 1.00±0.54 to 0.56±0.09 (P<0.05), andknockdown of HK2 in HCC cells decreased the number of invaded cells form 345±42 to 215±34 (P<0.05). The expression of epithelial markers ZO-1 and E-cadherin were up-regulated, while mesenchymal markers vimentin and N-cadherin were down-regulated in HCC cells when HK2 was knockeddown. Conclusions: HK2 is up-regulated in HCC and promotes cell motility by stimulating EMT.