Hexokinase 2 Promotes Cell Proliferation and Tumor Formation through the Wnt/β-catenin Pathway-mediated Cyclin D1/c-myc Upregulation in Epithelial Ovarian Cancer

Background: HK2 is reported as a key mediator of aerobic glycolysis, associating with the malignant growth in many types of cancers. Methods: In this study, stimulation of HK2 expression was observed in ovarian carcinoma tissues, comparing with the normal ovarian tissues. Results: Both of in vitro and in vivo experiments demonstrated that HK2 expression promoted the proliferation and tumor formation by accelerating cell cycle progression in ovarian cancer cells. Further research showed that HK2 expression enhanced the activity of Wnt/β-catenin signaling pathway, inducing the protein levels of β-catenin, c-myc and CyclinD1 in HK2 over-expressing OVCA433 and SKOV3 cells. The positive correlation between HK2 and β-catenin, c-myc, CyclinD1 in human ovarian cancer were confirmed from the GEPIA online database. When β-catenin expression was blocked by an inhibitor (XAV939), reduced c-myc and CyclinD1 expression was observed in HK2 over-expressing cells, with inhibited cell growth. Conclusion: Our data demonstrated that hexokinase 2 promotes cell proliferation and tumor formation through the Wnt/β-catenin pathway-mediated CyclinD1/c-myc upregulation in human ovarian cancer.