A NOVEL ROLE OF GELSOLIN IN CANCER CELL SURVIVAL THROUGH REGULATION OF FIBRONECTIN

Abstract

ACTIN CYTOSKELETON PLAYS AN IMPORTANT ROLE IN EXTRACELLULAR MATRIX-INDEPENDENT SURVIVAL OR ANOIKIS RESISTANCE OF CANCER CELLS, WITH UNKNOWN MODES OF ACTION. IN THIS STUDY, WE SHOWED THAT GELSOLIN, A KNOWN-REGULATOR OF ACTIN CYTOSKELETON, PROTECTED COLORECTAL CANCER HCT 116 CELLS FROM APOPTOSIS AND PROMOTED HCT 116 CELL SURVIVAL IN AN ANOIKIS MODEL. GELSOLIN EXERTED THE EFFECTS BY UPREGULATING FIBRONECTIN EXPRESSION AND SECRETION IN HCT 116 CELLS. FIBRONECTIN RESCUED THE APOPTOTIC EFFECTS OF GELSOLIN KNOCK-DOWN IN CELLS CULTURED IN THE ANOIKIS CONDITION AND PROMOTED CANCER CELL SURVIVAL THROUGH AKT SIGNALING. OUR RESULTS ALSO SUGGESTED THAT GELSOLIN UPREGULATED FIBRONECTIN EXPRESSION IN HCT 116 CELLS THROUGH ACTIVATION OF THE TRANSCRIPTION FACTOR NUCLEAR FACTOR KAPPA B (NFKAPPB) BUT NOT THROUGH THE EARLY GROWTH RESPONSE PROTEINS 1 (EGR-1). IN SUMMARY, OUR FINDINGS REVEAL A NOVEL ROLE OF GELSOLIN IN PROMOTING CANCER CELL SURVIVAL IN AN ANOIKIS CONDITION BY UPREGULATING FIBRONECTIN EXPRES