ADP-ribosylation of the G protein Rho inhibits integrin regulation of tumor cell growth.
Using a gastric derived tumor line, we investigated the involvement of beta 1 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 G0/G1 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-beta 1 integrin monoclonal antibodies. Phospholipid levels were induced upon beta 1 integrin-mediated adhesion to collagen, and the phospholipid induction was inhibited by either antibodies to beta 1 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 tumour growth in response to matrix.
Udagawa
T
T
Department of Immunology, University of Texas, M.D. Anderson Cancer Center, Houston 77030, USA.
McIntyre
B W
BW
D036002:ADP Ribose Transferases / Q000378:metabolism / Q000494:pharmacology; D000246:Adenosine Diphosphate Ribose / Q000378:metabolism*; D001905:Botulinum Toxins; D002384:Catalysis; D002448:Cell Adhesion; D002455:Cell Division; D002461:Cell Line, Transformed; D016213:Cyclins / Q000378:metabolism; D016193:G1 Phase; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D010743:Phospholipids / Q000096:biosynthesis / Q000378:metabolism; D016192:Resting Phase, Cell Cycle; D014407:Tumor Cells, Cultured
D016213:Cyclins; D016023:Integrins; D010743:Phospholipids; D000246:Adenosine Diphosphate Ribose; D036002:ADP Ribose Transferases; C063007:exoenzyme C3, Clostridium botulinum; D001905:Botulinum Toxins; D019204:GTP-Binding Proteins