Ca-dependent demethylation of phosphatase PP2Ac promotes glucose deprivation-induced cell death independently of inhibiting glycolysis.

Abstract in brief

• Glucose deprivation triggers a specific cell death pathway in certain cancer cells involving plasma membrane depolarization, calcium influx, and activation of kinases like RIPK1 and CAMK1, leading to the demethylation and inactivation of PP2A phosphatase.
• This cell death process occurs independently of glycolysis inhibition, as it can be initiated even by nonmetabolizable glucose analogs like 2-deoxyglucose, suggesting glucose acts as a signaling molecule beyond its metabolic role.
• Targeting components of this pathway, such as the demethylation process or calcium channels, could offer new therapeutic strategies for selectively killing cancer cells sensitive to glucose withdrawal.]