Requirement of hypoxia-inducible factor 1 alpha for interleukin 1 beta induced glycolysis in colorectal cancer cells.

The research elucidates the role of hypoxia-inducible factor 1 alpha (HIF1) and AKT1/2 in the stimulation of glycolysis in colorectal cancer cells, following the administration of interleukin-1 beta (IL-1β). This pro-inflammatory cytokine is often elevated in colorectal cancer and prompts the cells to boost glycolysis, while curbing the oxidation of butyrate, a nutrient derived from fiber.

The study indicates that IL-1β facilitates glycolysis and curtails mitochondrial respiration. Moreover, it elevates the phosphorylation of both AKT and HIF1. To further investigate this, colorectal cancer cells deficient in either AKT1/2 or HIF1 were used, which highlighted the necessity of these proteins in the glycolysis induction pathway.

Notably, AKT1/2 was found to precede HIF1, as IL-1β could still boost AKT phosphorylation even without HIF1. However, the absence of AKT1/2 impeded IL-1β's ability to increase HIF1 protein levels. Additionally, the research underscores that tumor necrosis factor alpha (TNF), another cytokine frequently present in colorectal cancer, also augments glycolysis in a manner dependent on AKT and HIF1.

The findings suggest a shared pathway involving AKT activation and HIF1 upregulation, through which pro-inflammatory cytokines like IL-1β and TNF enhance glycolysis in colorectal cancer cells, fostering cancer progression.