SIALYLATION OF INTEGRIN beta 1 IS INVOLVED IN RADIATION-INDUCED ADHESION AND MIGRATION IN HUMAN COLON CANCER CELLS

Abstract

Purpose: Previously, we reported that radiation-induced ST6 Gal I gene expression was responsible for an increase of integrin beta 1 sialylation. In this study, we have further investigated the function of radiation-mediated integrin beta 1 sialylation in colon cancer cells. Methods and Materials: We performed Western blotting and lectin affinity assay to analyze the expression and level of sialylated integrin beta 1. After exposure to ionizing radiation (IR), adhesion and migration of cells were measured by in vitro adhesion and migration assay. Results: IR increased sialylation of integrin beta 1 responsible for its increased protein stability and adhesion and migration of colon cancer cells. However, for cells with an N-glycosylation site mutant of integrin beta 1 located on the I-like domain (Mu3), these effects were dramatically inhibited. In addition, integrin beta 1 mediated radioresistance was not observed in cells containing this mutant. When sialylation of integrin beta 1 was targeted with a sulfonamide chalcone compound, inhibition of radiation-induced sialylation of integrin beta 1 and inhibition of radiation-induced adhesion and migration occurred. Conclusion: The increase of integrin beta 1 sialylation by ST6 Gal I is critically involved in radiation-mediated adhesion and migration of colon cancer cells. From these findings, integrin beta 1 sialylation may be a novel target for overcoming radiation-induced survival, especially radiation-induced adhesion and migration. (C) 2010 Elsevier Inc.