The Warburg effect is a key metabolic feature of cancer cells and manifests as substantially increased glycolysis regardless of the presence of oxygen[1].The initial step of glycolysis is catalyzed by hexokinase(HK),w...The Warburg effect is a key metabolic feature of cancer cells and manifests as substantially increased glycolysis regardless of the presence of oxygen[1].The initial step of glycolysis is catalyzed by hexokinase(HK),which converts glucose to the metabolic intermediate glucose-6-phosphate(G-6-P).Four kinds of HK isozymes,HK1,HK2,HK3 and HK4,have been found in mammals.HK1 and HK2 bind to the mitochondrial outer membrane through interac-tions with voltage-dependent anion channels(VDACs),and both of thesemolecules have a high affinity for glucose[2].HK2 overexpression is frequently detected in cancer cells,leading to enhanced aerobic glycolysis and tumorigenesis that renders HK2 an attractive target for cancer treatment[3].Important advances in research on cancer metabolism in recent decades have revealed thatmetabolic enzymes have non-metabolic functions,which play pivotal roles in tumor development and progression[4–6].Recent studies uncovered that HK2 directly promoted tumor immune evasion through the activity of a previously unidentified protein kinase and tumor cell stemness via upregulation of CD133 expression.展开更多
基金Ministry of Science and Technology of the People’s Republic of China,Grant/Award Number:2020YFA0803300National Natural Science Foundation of China,Grant/Award Numbers:82188102,82030074,81902423+1 种基金Zhejiang Natural Science Foundation Key Project,Grant/Award Number:LD21H160003Leading Innovative and Entrepreneur Team Introduction Program of Zhejiang,Grant/Award Number:2019R01001。
文摘The Warburg effect is a key metabolic feature of cancer cells and manifests as substantially increased glycolysis regardless of the presence of oxygen[1].The initial step of glycolysis is catalyzed by hexokinase(HK),which converts glucose to the metabolic intermediate glucose-6-phosphate(G-6-P).Four kinds of HK isozymes,HK1,HK2,HK3 and HK4,have been found in mammals.HK1 and HK2 bind to the mitochondrial outer membrane through interac-tions with voltage-dependent anion channels(VDACs),and both of thesemolecules have a high affinity for glucose[2].HK2 overexpression is frequently detected in cancer cells,leading to enhanced aerobic glycolysis and tumorigenesis that renders HK2 an attractive target for cancer treatment[3].Important advances in research on cancer metabolism in recent decades have revealed thatmetabolic enzymes have non-metabolic functions,which play pivotal roles in tumor development and progression[4–6].Recent studies uncovered that HK2 directly promoted tumor immune evasion through the activity of a previously unidentified protein kinase and tumor cell stemness via upregulation of CD133 expression.
