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Hexokinase 2 in Cancer: A Prima Donna Playing Multiple Characters
Francesco Ciscato1, Lavinia Ferrone1, Ionica Masgras1,2
1Dipartimento di Scienze Biomediche, Università di Padova, 35131 Padova, Italy.
International Journal of Molecular Sciences
|May 5, 2021
Summary
Hexokinase 2 (HK2) is crucial for tumor growth by linking metabolism and survival pathways at mitochondria-associated membranes (MAMs). Targeting HK2
Area of Science:
- Biochemistry and Molecular Biology
- Cancer Metabolism
- Cellular Signaling
Background:
- Hexokinases (HKs) are enzymes that phosphorylate glucose, initiating its intracellular metabolism.
- Hexokinase 2 (HK2) is highly expressed in neoplastic cells, promoting aerobic glycolysis and tumor growth.
- HK2 exhibits functions beyond glycolysis, including regulation of autophagy and cell death, particularly when localized to mitochondria.
Purpose of the Study:
- To investigate the role of HK2 localization at Mitochondria-Associated Membranes (MAMs) in tumor progression.
- To elucidate the function of HK2 at MAMs as a nexus for metabolic and survival pathways.
- To explore the potential of targeting HK2 subcellular localization as an anti-cancer strategy.
Main Methods:
- Analysis of HK2 expression and localization in tumor cells.
- Investigating HK2's role in regulating intracellular calcium (Ca2+) fluxes at MAMs.
- Evaluating the impact of disrupting HK2 localization on neoplastic progression and survival pathways.
Main Results:
- HK2 localizes to MAMs in tumor cells, sites of contact between mitochondria and endoplasmic reticulum.
- MAM-localized HK2 plays a critical role in regulating intracellular Ca2+ dynamics.
- This localization positions HK2 as a key intersection point for metabolic reprogramming and cell survival mechanisms in cancer.
Conclusions:
- HK2's presence at MAMs is essential for sustaining tumor cell progression.
- HK2 at MAMs integrates metabolic pathways with cell survival signaling.
- Targeting HK2's subcellular localization offers a novel therapeutic strategy against cancer.
Keywords:
Ca2+MAMsapoptosiscell-penetrating peptideschemotherapeuticshexokinase 2mitochondriatumor metabolismMore Related Videos
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