Schwartz M A, Toksoz D, Khosravi-Far R
Department of Vascular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
EMBO J. 1996 Dec 2;15(23):6525-30.
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.
生长因子受体信号通路的组成性激活会导致生长失控，但肿瘤细胞为何变得不依赖贴壁生长却不太清楚。整合素传递细胞生长所需信号这一事实表明，整合素下游步骤的组成性激活介导了不依赖贴壁生长。由于小GTP酶Rho可能介导整合素信号转导，因此研究了血清以及Rho核苷酸交换因子癌基因dbl和lbc对细胞生长和信号通路的影响。我们的数据表明，这些癌基因诱导不依赖贴壁但依赖血清的生长以及信号通路的激活。因此，这些结果表明，不依赖贴壁生长是由整合素依赖性信号事件的组成性激活导致的。它们还支持Rho是整合素信号在功能上重要的介导因子这一观点。
