Transformation by Rho exchange factor oncogenes is mediated by activation of an integrin-dependent pathway.
Constitutive activation of growth factor receptor signaling pathways leads to uncontrolled growth, but why tumor cells become anchorage independent is less clear. The fact that integrins transmit signals required for cell growth suggests that constitutive activation of steps downstream from integrins mediates anchorage independence. Since the small GTPase Rho may mediate integrin signal transduction, the effects of serum and the Rho nucleotide exchange factor oncogenes dbl and lbc on cell growth and signaling pathways were examined. Our data show that these oncogenes induce anchorage-independent but serum-dependent growth and stimulation of signaling pathways. These results show, therefore, that anchorage-independent growth results from constitutive activation of integrin-dependent signaling events. They also support the view that Rho is a functionally important mediator of integrin signaling.
Schwartz
M A
MA
Department of Vascular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Toksoz
D
D
Khosravi-Far
R
R
D016475:3T3 Cells; D054758:A Kinase Anchor Proteins; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002455:Cell Division; D002471:Cell Transformation, Neoplastic; D019204:GTP-Binding Proteins / Q000378:metabolism*; D020662:Guanine Nucleotide Exchange Factors; D016023:Integrins / Q000502:physiology*; D007700:Kinetics; D051379:Mice; D015778:Minor Histocompatibility Antigens; D008954:Models, Biological; D009857:Oncogenes; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D015682:Retroviridae Proteins, Oncogenic / Q000096:biosynthesis*; D015398:Signal Transduction; D013917:Thrombin / Q000494:pharmacology; D020741:rho GTP-Binding Proteins
D054758:A Kinase Anchor Proteins; C085467:AKAP13 protein, human; D048868:Adaptor Proteins, Signal Transducing; D020662:Guanine Nucleotide Exchange Factors; D016023:Integrins; C512843:Mcf2 protein, mouse; D015778:Minor Histocompatibility Antigens; D019269:Phosphatidylinositol 4,5-Diphosphate; D011518:Proto-Oncogene Proteins; D015682:Retroviridae Proteins, Oncogenic; D013917:Thrombin; D019204:GTP-Binding Proteins; D020741:rho GTP-Binding Proteins; D002118:Calcium