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

Oncogene
P A J MullerKaren H Vousden

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.

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Citations

Nov 20, 2013·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Javier E GirardiniGiannino Del Sal
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Methods Mentioned

BETA
MDA
co-immunoprecipitation
xenografts
FCS
confocal microscopy
ELISA
transfection
enzyme-linked immunosorbent assays
pulldown
enzyme-linked immunosorbent assay

Software Mentioned

MaxQuant
Andromeda
Velocity
ImageJ

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