A NOVEL ROLE OF GELSOLIN IN AUTOPHAGY AND CANCER CELL SURVIVIAL

DENG SHUO

Publication

A NOVEL ROLE OF GELSOLIN IN AUTOPHAGY AND CANCER CELL SURVIVIAL

DENG SHUO

Abstract

GELSOLIN IS A MULTIFUNCTIONAL ACTIN REGULATORY PROTEIN KNOWN TO BE DYSREGULATED IN VARIOUS CANCERS. IT HAS BEEN PREVIOUSLY SHOWN THAT GELSOLIN PLAYS A ROLE IN APOPTOSIS AND THUS RESISTANCE TO CHEMOTHERAPY, HOWEVER, THE UNDERLYING MECHANISMS HAVE NOT BEEN FULLY UNDERSTOOD. INDEPENDENT LINES OF STUDY SUGGEST THAT THE ACTIN CYTOSKELETON AND ITS REGULATORY PROTEINS REGULATE AUTOPHAGY, A LYSOSOME-MEDIATED SELF-DIGESTIVE PROCESS WHICH CAN EXERT CYTOPROTECTIVE EFFECTS AGAINST STRESSES. IT IS THEREFORE CONCEIVABLE THAT GELSOLIN COULD PROTECT CELLS FROM STRESSES VIA MODULATING AUTOPHAGY. IN THIS STUDY, WE SHOWED THAT STABLE OVEREXPRESSION OF GELSOLIN IN HCT116 CELLS INCREASED CELL SURVIVAL UNDER STARVATION AND 5-FLUOROURACIL TREATMENT, WHILE KNOCKDOWN OF GELSOLIN SENSITIZED CELLS TO THESE TREATMENTS. IN RESPONSE TO THESE STRESSES, GELSOLIN-OVEREXPRESSING CELLS SHOWED INCREASED AUTOPHAGIC LEVELS WHILST GELSOLIN KNOCKDOWN CELLS POSSESSED LOWER LEVELS OF AUTOPHAGY. INHIBITION OF AUTOPHAGY VIA LYSO