INPP4B-mediated tumor resistance is associated with modulation of glucose metabolism via hexokinase 2 regulation in laryngeal cancer cells

Abstract

Inositol polyphosphate 4-phosphatase type II (INPP4B) was recently identified as a tumor resistance factor in laryngeal cancer cells. Herein, we show that INPP4B-mediated resistance is associated with increased glycolytic phenotype. INPP4B expression was induced by hypoxia and irradiation. Intriguingly, overexpression of INPP4B enhanced aerobic glycolysis. Of the glycolysis-regulatory genes, hexokinase 2 (HK2) was mainly regulated by INPP4B and this regulation was mediated through the Akt-mTOR pathway. Notably, codepletion of INPP4B and HK2 markedly sensitized radioresistant laryngeal cancer cells to irradiation or anticancer drug. Moreover, INPP4B was significantly associated with HK2 in human laryngeal cancer tissues. Therefore, these results suggest that INPP4B modulates aerobic glycolysis via HK2 regulation in radioresistant laryngeal cancer cells.

Keywords: ERK-1/2; FDG; Glycolysis; HIF-1α; HK2; INPP4B; Laryngeal cancer; PI3K; PTEN; RR-HEp-2; Tumor resistance; extracellular signal-regulated protein kinase-1/2; fluorodeoxyglucose; hexokinase 2; hypoxia-inducible factor-1α; inositol polyphosphate 4-phosphatase Type II; phosphatase and tensin homolog; phosphoinositide 3-kinases; radioresistant HEp-2; siRNA; small interfering RNA.