Hexokinase 2 in Cancer: A Prima Donna Playing Multiple Characters

被引:172
作者
Ciscato, Francesco [1 ]
Ferrone, Lavinia [1 ]
Masgras, Ionica [1 ,2 ]
Laquatra, Claudio [1 ]
Rasola, Andrea [1 ]
机构
[1] Univ Padua, Dipartimento Sci Biomed, I-35131 Padua, Italy
[2] CNR, Inst Neurosci, I-56124 Pias, Italy
关键词
hexokinase; 2; mitochondria; MAMs; Ca2+; tumor metabolism; apoptosis; chemotherapeutics; cell-penetrating peptides; PERMEABILITY TRANSITION PORE; CELL PENETRATING PEPTIDES; ENDOPLASMIC-RETICULUM; HEPATOCELLULAR-CARCINOMA; ENERGY-METABOLISM; PROGNOSTIC-FACTOR; MOUSE MODELS; HK-II; MITOCHONDRIA; APOPTOSIS;
D O I
10.3390/ijms22094716
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Hexokinases are a family of ubiquitous exose-phosphorylating enzymes that prime glucose for intracellular utilization. Hexokinase 2 (HK2) is the most active isozyme of the family, mainly expressed in insulin-sensitive tissues. HK2 induction in most neoplastic cells contributes to their metabolic rewiring towards aerobic glycolysis, and its genetic ablation inhibits malignant growth in mouse models. HK2 can dock to mitochondria, where it performs additional functions in autophagy regulation and cell death inhibition that are independent of its enzymatic activity. The recent definition of HK2 localization to contact points between mitochondria and endoplasmic reticulum called Mitochondria Associated Membranes (MAMs) has unveiled a novel HK2 role in regulating intracellular Ca2+ fluxes. Here, we propose that HK2 localization in MAMs of tumor cells is key in sustaining neoplastic progression, as it acts as an intersection node between metabolic and survival pathways. Disrupting these functions by targeting HK2 subcellular localization can constitute a promising anti-tumor strategy.
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页数:14
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