THE ROLE OF THE ROLE OF ASCC3 IN THE ENERGY METABOLISM AND CHEMO RESPONSE OF HUMAN COLON CANCER CELLS

Abstract

ASCC3 is a multifunctional protein implicated in various cellular processes. ASCC3 is one of four subunits of the activating signal co-integrator 1 complex with established functions in DNA repair and protein quality control pathways. Published proteomic studies suggest that ASCC3 may regulate metabolic processes since the ASCC3 interactome includes mitochondria proteins and metabolic enzymes. However, whether ASCC3 regulates energy metabolism has not been characterized. Using a panel of colorectal cancer cell lines, I have shown that loss of ASCC3 leads to reprogramming of energy metabolism, favoring OxPhos but inhibiting glycolysis in colorectal cancer cells. I have further demonstrated that loss of ASCC3 promotes chemoresistance in colorectal cancer cells, agreeing with TCGA patient data that ASCC3 expression is directly correlated with a survival probability in patients with colorectal cancer. These results altogether suggest that loss of ASCC3 promotes chemoresistance in colorectal cancer cells, at least in part by reprogramming energy metabolism. These results further underscore ASCC3 as a prognostic marker in CRC patients.