Journal
JOURNAL OF CELL BIOLOGY
Volume 155, Issue 3, Pages 459-470Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.200106070
Keywords
cell adhesion; apoptosis; caspase; integrin; ligands
Categories
Funding
- NCI NIH HHS [CA45726, CA50286, CA78045, R01 CA045726, R01 CA050286, R37 CA050286, P01 CA078045] Funding Source: Medline
- NIAMS NIH HHS [AR02089] Funding Source: Medline
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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.
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