High expression of hexokinase 2 promotes lung cancer proliferation and metastasis.

Introduction: High metabolic plasticity, as one of the hallmarks of multiple cancers, usually promotes cancer growth and metastasis. Therefore, metabolic enzymes could be selective targets in suppressing the growth and invasion of cancer cells. It is generally believed that hexokinase 2 (HK2) catalysing glucose into glucose-6-phosphate is the first step in glucose metabolism. It is unclear, however, if HK2 is involved in lung cancer (LC) proliferation and metastasis. Material and methods: Tumours and adjacent tissue from LC patients were used to study the expression of HK2 by RT-PCR and western blot analysis. Several different LC cell lines were used to explore the oncogene function of HK2 via MTS and BrdU assay Results: HK2 was upregulated in primary LC tissue and metastatic foci. The expression of HK2 can be modulated by multiple mutations of oncogenes or tumour suppressors, including Kras, p53, and Keap1. Functionally, suppression of HK2 expression by shRNA transfection in LC cell lines hindered lactate production and therefore suppressed cell migration and invasion. The depletion of HK2 also sensitised the LC cells to cisplatin-induced apoptosis, suggesting that HK2 also mediated the chemoresistance in LC. Finally, our Conclusions: We demonstrated that HK2 is required for LC cell growth and metastasis