ADP-ribosylation of the G Protein Rho Inhibits Integrin Regulation of Tumor Cell Growth

doi:10.1074/jbc.271.21.12542

ADP-ribosylation of the G Protein Rho Inhibits Integrin Regulation of Tumor Cell Growth (*)

From the Department of Immunology, The University of Texas, M. D. Anderson Cancer Center, Houston, Texas 77030

^§ To whom correspondence should be addressed:
Dept. of Immunology, Box 180, The University of Texas, M. D. Anderson Cancer Center, Houston, TX 77030
. Tel.: 713-792-8739; Fax: 713-745-0846.

Abstract

Using a gastric derived tumor line, we investigated the involvement of β1 integrin and Rho in cell growth regulation in response to collagen. The addition of C3 exoenzyme from Clostridium botulinum to specifically ribosylate and inhibit the function of the rho gene products inhibited cellular proliferation in a dose-dependent fashion. C3 exoenzyme exhibited broad cytostatic activity toward a number of tumor lines and induced G/G accumulation, cyclin A inhibition, and pronounced alterations in cell morphology. Integrin-mediated adhesion to collagen led to the expression of the cyclin A gene whose expression could be blocked using anti-β1 integrin monoclonal antibodies. Phospholipid levels were induced upon β1 integrin-mediated adhesion to collagen, and the phospholipid induction was inhibited by either antibodies to β1 integrin or pretreatment of cells with C3 exoenzyme. Significant reduction in phospholipid levels correlated with proliferation for a panel of tumor lines deprived of adhesion to substrate. These results implicate a novel role for integrins and Rho in the regulation of tumor growth in response to matrix.

Footnotes

↵* This work was supported by National Institutes of Health Grant 62596. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
↵() The abbreviations used are:

FBS

fetal bovine serum

PBS

phosphate-buffered saline

polyHEMA

poly(2-hydroxyethyl methacrylate)

PIP

phosphatidylinositol phosphate

PIP

phosphatidylinositol bisphosphate.
↵⁽⁾ Dillon, S. T., and Feig, L. A.(1995) Methods Enzymol.256, 174-184.
- Received August 24, 1995.
- Revision received March 1, 1996.