Activated K-ras is involved in regulation of integrin expression in human colon carcinoma cells

Abstract

Integrins participate in controlling proliferation and migration. Therefore, changes in integrin expression might be responsible for unrestrained proliferation and invasiveness of tumor cells. Alterations of integrin subunit expression have been observed in human colon carcinoma, especially loss or reduction of the α5 subunit, which was observed consistently. The mechanisms responsible for reduction of α5 expression and alteration of expression of other integrins are not fully understood. Circumstantial evidence from previous investigations points to an involvement of activated ras oncogenes in repression of integrin expression. The K-ras protooncogene is activated by point mutation in 50% of human colon carcinomas. Thus, we choose an antisense approach for specific inactivation of activated K-ras in the human colon carcinoma cell line SW 480 in order to test whether activated K-ras contributes to changes in integrin expression on colon carcinoma cells. Cell surface expression of the αl and the α5 subunit was increased in K-ras antisense transfected clones, cell surface expression of the α3 subunit and the αv subunit was decreased. This shows, in a human system, that activated K-ras is involved in diminishing cell surface expression of the αlβl collagen/laminin receptor and the α5βl fibronectin receptor, both of which are implicated in maintenance of a non-transformed phenotype. Moreover, activated K-ras contributes to increased cell surface expression of the α3βl laminin/collagen/fibronectin receptor and the αvβ5 vitronectin receptor, which might play a role in metastatic behavior of tumor cells. (C) 2000 Wiley-Liss, Inc.