Hexokinase II: Cancer's double-edged sword acting as both facilitator and gatekeeper of malignancy when bound to mitochondria

By Saroj P. Mathupala, Y. Ko, P. Pedersen. Oncogene, 2006

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Reprogramming of glucose, fatty acid and amino acid metabolism for cancer progression (2015, background): “Glucose across the plasma membrane mediated by glucose transporters is rapidly phosphorylated by hexokinase (primarily HK II) bound to the outer mitochondrial membrane via the voltage-dependent anion channel, which allows direct access to HK II of ATP generated by the ATP synthase and transported ac”
Metformin, Independent of AMPK, Inhibits mTORC1 In a Rag GTPase-Dependent Manner (2010, background): “In most tumor cells, under aerobic conditions, glycolysis is upregulated to generate glycolytic intermediates, required as biosynthetic building blocks (Mathupala et al., 2006, 2009).”
Tumor glycolysis as a target for cancer therapy: progress and prospects (2013, background): “brane) plays a pivotal role in the energy metabolism of cancer cells [86,87].”
Phosphate-activated glutaminase (GLS2), a p53-inducible regulator of glutamine metabolism and reactive oxygen species (2010, background): “Nevertheless, some studies report that p53 canpromote at least some steps in glycolysis (9, 10).”
Aerobic glycolysis: meeting the metabolic requirements of cell proliferation. (2011, positive): “However, cancer cells frequently overexpress HK II (Mathupala et al 2006), and at least some glioblastoma cells are specifically dependent on HK II over other isoforms of the enzyme (Wolf et al 2011).”