THE ROLE OF PROTEIN PHOSPHATASE 2A IN CANCER CELL DEATH UPON GLUCOSE DEPRIVATION

Abstract

ONE OF THE HALLMARKS OF CANCER CELLS IS ALTERED GLUCOSE METABOLISM. INTERESTINGLY, A SUBSET OF TUMOR TYPES RESPOND TO GLUCOSE DEPRIVATION BY UNDERGOING CELL DEATH. NOT MUCH IS KNOWN REGARDING THE PATHWAYS THAT MEDIATE GLUCOSE DEPRIVATION INDUCED CELL DEATH IN DIFFERENT TUMOR TYPES. HERE, I SHOW THAT PROTEIN PHOSPHATASE 2A (PP2A) HAS A POTENTIAL ROLE IN SENSING LOW LEVELS OF GLUCOSE IN CANCER CELLS. GLUCOSE DEPRIVATION INITIATES AN INFLUX OF CALCIUM TO THE CYTOPLASM WHICH ACTIVATES THE CALCIUM-CALMODULIN DEPENDENT KINASE CAMK1. WE SHOW THAT DEMETHYLATION OF THE PP2A CATALYTIC SUBUNIT IS CRITICAL FOR GLUCOSE DEPRIVATION INDUCED CELL DEATH AND THIS CELL DEATH PATHWAY IS VIA NECROSIS. THESE DATA PROVIDE INSIGHTS ON A NOVEL PATHWAY IN CANCER GLUCOSE METABOLISM AND THAT COULD BE EXPLOITED FOR THERAPEUTIC PURPOSES.