Work

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

Year: 2001

Type: article

Abstract: 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.

Source: The Journal of Cell Biology

DOI: 10.1083/jcb.200106070

Authors: Dwayne G. Stupack, Xose S. Puente, Souphaphone Boutsaboualoy, Chris M. Storgard, David A. Cheresh

Institution: Scripps Research Institute

Language: English

Topic: Cell Adhesion Molecules Research

Subfield: Immunology and Allergy

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green

Funders: National Institutes of Health, National Cancer Institute, National Institute of Arthritis and Musculoskeletal and Skin Diseases