Apoptosis of adherent cells by recruitment of caspase-8 to unligated integrins

作者：Dwayne G. Stupack, Xosé S. Puente, Souphaphone Boutsaboualoy, Chris M. Storgard, David A. Cheresh · 发表于：The Journal of Cell Biology · 年份：2001 · DOI：10.1083/jcb.200106070 · 被引用次数：552 · 研究领域：Cell Adhesion Molecules Research、Cell death mechanisms and regulation、Phagocytosis and Immune Regulation

Integrin-mediated adhesion promotes cell survival in vitro, whereas integrin antagonists induce apoptosis of adherent cells in vivo. Here, we demonstrate that cells adherent within a three-dimensional extracellular matrix undergo apoptosis due to expression of unligated integrins, the beta subunit cytoplasmic domain, or its membrane proximal sequence KLLITIHDRKEF. Integrin-mediated death requires initiator, but not stress, caspase activity and is distinct from anoikis, which is caused by the loss of adhesion per se. Surprisingly, unligated integrin or beta integrin tails recruit caspase-8 to the membrane, where it becomes activated in a death receptor-independent manner. Integrin ligation disrupts this integrin-caspase containing complex and increases survival, revealing an unexpected role for integrins in the regulation of apoptosis and tissue remodeling.