Endosomal integrin signals for survival

Rainero, E. and Norman, J. C. (2015) Endosomal integrin signals for survival. Nature Cell Biology, 17(11), pp. 1373-1375. (doi: 10.1038/ncb3261) (PMID:26515017)

Abstract

Many epithelial and mesenchymal cells rely on integrin-mediated contact with the extracellular matrix (ECM) for growth and survival1. Therefore, when anchorage-dependent cells become detached from the ECM they cease to thrive and begin to die through a form of programmed cell death called anoikis1. When cells are attached to the matrix, integrins engage with the ECM and cluster at the plasma membrane to form large macromolecular signalling machines termed focal adhesions or focal contacts. Clustering of ligand-engaged integrins into focal adhesions promotes recruitment of signalling molecules such as focal adhesion kinase (FAK), and cytoskeletal adaptor proteins such as talin, to the integrin cytoplasmic domain (Fig. 1a)2. These adaptors, in turn, mediate mechanical links to the actin cytoskeleton to allow force transmission, but also bring in numerous signalling moieties that lead to activation of pathways that support cell growth and suppress anoikis3, 4. Prominent integrin-activated signalling pathways are the Ras–PI3K–PDK1–Akt and Ras–Raf–MEK–ERK axes and, although the mechanistic details of how integrin engagement leads to their activation remain somewhat obscure, there is copious evidence that following cell detachment the activity of these pathways is reduced, and this increases the likelihood of cells entering anoikis3, 4. In this issue of Nature Cell Biology Alanko et al.5 report the existence of an integrin-dependent pathway that mediates anoikis resistance. They show that internalized integrins trigger the assembly of endosomal signalling complexes that include FAK, to foster cancer cell survival and to promote metastatic growth.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Norman, Professor James and Rainero, Ms Elena
• Authors: Rainero, E., and Norman, J. C.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Nature Cell Biology
• Publisher: Nature Publishing Group
• ISSN: 1465-7392
• ISSN (Online): 1476-4679