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Binding of cell surface integrins to the extracellular matrix (ECM) stimulates a variety of intracellular signalling pathways. Integrin signalling can activate the PI 3-kinase and MAP kinase pathways, for example, and thereby induce cells to proliferate; however, it can also stimulate apoptosis. In a Commentary on p. 3729, Dwayne Stupack and David Cheresh discuss the different ways in which integrins tip the balance between cell survival and cell death. The simplest case is perhaps anoikis, in which the absence of a survival signal provided by integrin anchorage leads to apoptosis. Integrin signalling can also induce resistance to apoptotic stimuli directly through pathways that target the Bcl-2 and IAP families of apoptosis regulators and death effector domain (DED) proteins. Alternatively, it can promote `integrin-mediated death', and this appears to depend on the context of the binding event (i.e. whether the integrin ligand is soluble or substrate immobilized). Integrins can thus act as biosensors that respond to specific ECM compositions by generating death or survival signals appropriate for maintenance of tissue architecture and remodelling during development and repair processes.
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