Autophagic targeting of Src promotes cancer cell survival following reduced FAK signalling

Sandilands, E. et al. (2012) Autophagic targeting of Src promotes cancer cell survival following reduced FAK signalling. Nature Cell Biology, 14(1), pp. 51-60. (doi:10.1038/ncb2386)

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Abstract

Here we describe a mechanism that cancer cells use to survive when flux through the Src/FAK pathway is severely perturbed. Depletion of FAK, detachment of FAK-proficient cells or expression of non-phosphorylatable FAK proteins causes sequestration of active Src away from focal adhesions into intracellular puncta that co-stain with several autophagy regulators. Inhibition of autophagy results in restoration of active Src at peripheral adhesions, and this leads to cancer cell death. Autophagic targeting of active Src is associated with a Src-LC3B complex, and is mediated by c-Cbl. However, this is independent of c-Cbl E3 ligase activity, but is mediated by an LC3-interacting region. Thus, c-Cbl-mediated autophagic targeting of active Src can occur in cancer cells to maintain viability when flux through the integrin/Src/FAK pathway is disrupted. This exposes a previously unrecognized cancer cell vulnerability that may provide a new therapeutic opportunity.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Vidal, Dr Marcos and Frame, Prof Margaret and Macagno, Mr Juan and McEwan, Mr David and Wilkinson, Dr Simon and Morton, Dr Jennifer and Brunton, Dr Valerie and Sansom, Professor Owen and Serrels, Dr Bryan and Sandilands, Ms Emma
Authors: Sandilands, E., Serrels, B., McEwan, D.G., Morton, J.P., Macagno, J.P., McLeod, K., Stevens, C., Brunton, V.G., Langdon, W.Y., Vidal, M., Sansom, O.J., Dikic, I., Wilkinson, S., and Frame, M.C.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Nature Cell Biology
ISSN:1465-7392
Published Online:04 December 2011

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