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

journal contribution
posted on 11.09.2018, 00:00 by PAJ Muller, AG Trinidad, P Timpson, JP Morton, S Zanivan, PVE Van Den Berghe, C Nixon, SA Karim, PT Caswell, JE Noll
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. © 2013 Macmillan Publishers Limited.

Funding

Category 2 - Other Public Sector Grants Category

History

Volume

32

Issue

10

Start Page

1252

End Page

1265

Number of Pages

14

eISSN

1476-5594

ISSN

0950-9232

Publisher

Nature Publishing Group

Additional Rights

CC BY-NC-ND 3.0

Peer Reviewed

Yes

Open Access

Yes

External Author Affiliations

Beatson Institute for Cancer Research; University of Manchester; University of Adelaide; Institute of Molecular and Cell Biology; p53 Laboratory (A-STAR)

Era Eligible

Yes

Journal

Oncogene

Exports

CQUniversity

Exports