Shaw L M, Rabinovitz I, Wang H H, Toker A, Mercurio A M
Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA.
Cell. 1997 Dec 26;91(7):949-60. doi: 10.1016/s0092-8674(00)80486-9.
We demonstrate that the alpha6beta4 integrin promotes carcinoma invasion through a preferential and localized targeting of phosphoinositide-3 OH kinase (PI3K) activity. Stable expression of alpha6beta4 increased carcinoma invasion in a PI3K-dependent manner, and transient expression of a constitutively active PI3K increased invasion in the absence of alpha6beta4. Ligation of alpha6beta4 stimulated significantly more PI3K activity than ligation of beta1 integrins, establishing specificity among integrins for PI3K activation. Alpha6beta4-regulated PI3K activity was required for the formation of lamellae, dynamic sites of motility, in carcinoma cells. The small G protein Rac is required downstream of PI3K for invasion. These studies define a mechanism by which the alpha6beta4 integrin promotes carcinoma invasion and invoke a novel function for PI3K signaling.
我们证明，α6β4整合素通过优先且局部地靶向磷酸肌醇-3-OH激酶（PI3K）活性来促进癌侵袭。α6β4的稳定表达以PI3K依赖的方式增加癌侵袭，而组成型活性PI3K的瞬时表达在不存在α6β4的情况下增加侵袭。α6β4的连接比β1整合素的连接刺激的PI3K活性明显更多，从而确立了整合素之间PI3K激活的特异性。α6β4调节的PI3K活性是癌细胞中片状伪足（动态运动位点）形成所必需的。小G蛋白Rac在PI3K下游是侵袭所必需的。这些研究定义了α6β4整合素促进癌侵袭的机制，并揭示了PI3K信号传导的新功能。
