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Hexokinase 2 in Cancer: A Prima Donna Playing Multiple Characters

1
Dipartimento di Scienze Biomediche, Università di Padova, 35131 Padova, Italy
2
Institute of Neuroscience, National Research Council, 56124 Pias, Italy
*
Authors to whom correspondence should be addressed.
Academic Editor: Athanasios G. Papavassiliou
Int. J. Mol. Sci. 2021, 22(9), 4716; https://doi.org/10.3390/ijms22094716
Received: 8 April 2021 / Revised: 26 April 2021 / Accepted: 26 April 2021 / Published: 29 April 2021
(This article belongs to the Special Issue Mitochondrial Functions, Alterations and Dynamics in Cancer)
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. View Full-Text
Keywords: hexokinase 2; mitochondria; MAMs; Ca2+; tumor metabolism; apoptosis; chemotherapeutics; cell-penetrating peptides hexokinase 2; mitochondria; MAMs; Ca2+; tumor metabolism; apoptosis; chemotherapeutics; cell-penetrating peptides
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MDPI and ACS Style

Ciscato, F.; Ferrone, L.; Masgras, I.; Laquatra, C.; Rasola, A. Hexokinase 2 in Cancer: A Prima Donna Playing Multiple Characters. Int. J. Mol. Sci. 2021, 22, 4716. https://doi.org/10.3390/ijms22094716

AMA Style

Ciscato F, Ferrone L, Masgras I, Laquatra C, Rasola A. Hexokinase 2 in Cancer: A Prima Donna Playing Multiple Characters. International Journal of Molecular Sciences. 2021; 22(9):4716. https://doi.org/10.3390/ijms22094716

Chicago/Turabian Style

Ciscato, Francesco, Lavinia Ferrone, Ionica Masgras, Claudio Laquatra, and Andrea Rasola. 2021. "Hexokinase 2 in Cancer: A Prima Donna Playing Multiple Characters" International Journal of Molecular Sciences 22, no. 9: 4716. https://doi.org/10.3390/ijms22094716

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