Aerobic glycolysis promotes tumor immune evasion and tumor cell stemness through the noncanonical function of hexokinase 2

[摘要] The Warburg effect is a key metabolic feature of cancercells and manifests as substantially increased glycolysisregardless of the presence of oxygen [1]. The initial step ofglycolysis is catalyzed by hexokinase (HK), which convertsglucose to the metabolic intermediate glucose-6-phosphate(G-6-P). Four kinds of HK isozymes, HK1, HK2, HK3 andHK4, have been found in mammals. HK1 and HK2 bindto the mitochondrial outer membrane through interactions with voltage-dependent anion channels (VDACs),and both of these molecules have a high affinity for glucose[2]. HK2 overexpression is frequently detected in cancercells, leading to enhanced aerobic glycolysis and tumorigenesis that renders HK2 an attractive target for cancertreatment [3]. Important advances in research on cancermetabolism in recent decades have revealed that metabolicenzymes have non-metabolic functions, which play pivotal roles in tumor development and progression [4–6].Recent studies uncovered that HK2 directly promotedtumor immune evasion through the activity of a previouslyunidentified protein kinase and tumor cell stemness viaupregulation of CD133 expression.

[学科分类] 社会科学、人文和艺术（综合）