Nuclear hexokinase 2 couples hyperglycemia to MYC-driven glycolytic and stemness programs in bladder cancer - PubMed

4 hours ago

Hyperglycemia is common in bladder cancer patients and linked to disease progression, with nuclear hexokinase 2 (HK2) identified as a key molecular link.
High glucose promotes HK2 nuclear translocation, where it binds MYC to form a transcriptional complex that activates glycolytic genes (e.g., HK2, LDHA) and stemness markers like CD44.
Inhibition of HK2 reduces high glucose-induced proliferation, colony formation, and glycolytic reprogramming in vitro, and lonidamine treatment mitigates tumor growth in hyperglycemic mouse models.
In human bladder cancer, HK2 expression correlates with MYC and LDHA levels and worse survival, especially in hyperglycemic patients, suggesting HK2 as a therapeutic target.

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