Mutant p53 enhances MET trafficking and signalling to drive cell scattering and invasion

Muller, P.A.J. et al. (2013) Mutant p53 enhances MET trafficking and signalling to drive cell scattering and invasion. Oncogene, 32(10), pp. 1252-1265. (doi: 10.1038/onc.2012.148)

Abstract

Tumour-derived mutant p53 proteins promote invasion, in part, by enhancing Rab coupling protein (RCP)-dependent receptor recycling. Here we identified MET as an RCP-binding protein and showed that mutant p53 promoted MET recycling. Mutant p53-expressing cells were more sensitive to hepatocyte growth factor, the ligand for MET, leading to enhanced MET signalling, invasion and cell scattering that was dependent on both MET and RCP. In cells expressing the p53 family member TAp63, inhibition of TAp63 also lead to cell scattering and MET-dependent invasion. However, in cells that express very low levels of TAp63, the ability of mutant p53 to promote MET-dependent cell scattering was independent of TAp63. Taken together, our data show that mutant p53 can enhance MET signalling to promote cell scattering and invasion through both TAp63-dependent and -independent mechanisms. MET has a predominant role in metastatic progression and the identification of mechanisms through which mutations in p53 can drive MET signalling may help to identify and direct therapy.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Norman, Professor James and Nixon, Mr Colin and Muller, Dr Patricia and Zanivan, Professor Sara and Timpson, Dr Paul and Caswell, Dr Patrick and Vousden, Karen and Morton, Professor Jen and Karim, Ms Saadia and Sansom, Professor Owen
• Authors: Muller, P.A.J., Trinidad, A.G., Timpson, P., Morton, J.P., Zanivan, S., van den Berghe, P.V.E., Nixon, C., Karim, S.A., Caswell, P.T., Noll, J.E., Coffill, C.R., Lane, D.P., Sansom, O.J., Neilsen, P.M., Norman, J.C., and Vousden, K.H.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Oncogene
• Publisher: Nature Publishing Group
• ISSN: 0950-9232
• ISSN (Online): 1476-5594
• Published Online: 12 May 2012
• Copyright Holders: Copyright © 2013 Macmillan Publishers Ltd.
• First Published: First published in Oncogene 32(10):1252-1265
• Publisher Policy: Reproduced under a Creative Commons License