Death by unligated integrin

Integrins have traditionally beenconsidered relatively indirect inducers of apoptosis, since integrin-mediated adhesion promotes cell survival, whereas inhibiting normal integrin signaling triggers cell death. Now on page 459, Stupack et al. describe an active integrin-mediated death pathway, a finding that helps explain seemingly contradictory earlier results from inhibitor studies and targeted gene disruptions.

The authors studied adherent cells in an artificial three-dimensional extracellular matrix, and found that expression of unligated integrins or integrin β subunit cytoplasmic domains in these cells induces apoptosis. The cells remained attached to the matrix while initiating cell death, distinguishing this integrin-mediated apoptotic pathway from anoikis, in which cells die after losing adherence. Instead, the unligated integrins recruit caspase 8 to the membrane and activate an apoptotic pathway that is independent of death receptors and distinct from stress-associated apoptosis.

Stupack et al. propose...