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

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dc.contributor.authorMuller, P.
dc.contributor.authorTrinidad, A.
dc.contributor.authorTimpson, P.
dc.contributor.authorMortin, J.
dc.contributor.authorZanivan, S.
dc.contributor.authorvan den Berghe, P.
dc.contributor.authorNixon, C.
dc.contributor.authorKarim, S.
dc.contributor.authorCaswell, P.
dc.contributor.authorNoll, J.
dc.contributor.authorCoffill, C.
dc.contributor.authorLane, D.
dc.contributor.authorSansom, O.
dc.contributor.authorNeilsen, P.
dc.contributor.authorNorman, J.
dc.contributor.authorVousden, K.
dc.date.issued2013
dc.description.abstractTumour-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.
dc.description.statementofresponsibilityPAJ Muller, AG Trinidad, P Timpson, JP Morton, S Zanivan, PVE van den Berghe, C Nixon, SA Karim, PT Caswell, JE Noll, CR Coffill, DP Lane, OJ Sansom, PM Neilsen, JC Norman and KH Vousden
dc.identifier.citationOncogene, 2013; 32(10):1252-1265
dc.identifier.doi10.1038/onc.2012.148
dc.identifier.issn0950-9232
dc.identifier.issn1476-5594
dc.identifier.orcidNoll, J. [0000-0001-7375-635X]
dc.identifier.urihttp://hdl.handle.net/2440/80793
dc.language.isoen
dc.publisherNature Publishing Group
dc.rights© 2013 Macmillan Publishers Limited All rights reserved
dc.source.urihttps://doi.org/10.1038/onc.2012.148
dc.subjectmutant p53
dc.subjectMET
dc.subjectrecycling
dc.titleMutant p53 enhances MET trafficking and signalling to drive cell scattering and invasion
dc.typeJournal article
pubs.publication-statusPublished

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