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HK3 (hexokinase 3) is a glucose-phosphorylating enzyme that
catalyzes the first committed step of glycolysis, converting glucose to
glucose-6-phosphate. HK3 is expressed prominently in hematopoietic and myeloid
cells but is also dysregulated in several cancers. Increased HK3 expression has
been associated with enhanced glycolytic activity, higher tumour grade,
immune-cell infiltration and poorer prognosis in cancers including glioma and
some hematologic malignancies. In glioma, high HK3 expression correlates with
malignancy and an immunosuppressive tumour microenvironment enriched in
macrophages and other infiltrating immune cells. However, HK3 can also support
antitumour immune-cell metabolism in certain contexts, so its biological effect
is not universally oncogenic. The typical tumour-associated direction is often
up, while the desired direct tumour-cell modulation is generally
down; immune-cell effects should be interpreted separately.
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