Cell
Volume 139, Issue 7, 24 December 2009, Pages 1327-1341
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Article
Mutant p53 Drives Invasion by Promoting Integrin Recycling

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Summary

p53 is a tumor suppressor protein whose function is frequently lost in cancers through missense mutations within the Tp53 gene. This results in the expression of point-mutated p53 proteins that have both lost wild-type tumor suppressor activity and show gain of functions that contribute to transformation and metastasis. Here, we show that mutant p53 expression can promote invasion, loss of directionality of migration, and metastatic behavior. These activities of p53 reflect enhanced integrin and epidermal growth factor receptor (EGFR) trafficking, which depends on Rab-coupling protein (RCP) and results in constitutive activation of EGFR/integrin signaling. We provide evidence that mutant p53 promotes cell invasion via the inhibition of TAp63, and simultaneous loss of p53 and TAp63 recapitulates the phenotype of mutant p53 in cells. These findings open the possibility that blocking alpha5/beta1-integrin and/or the EGF receptor will have therapeutic benefit in mutant p53-expressing cancers.

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Present address: The Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK

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Present address: UPMC Univ Paris 06, UMR 7150, Equipe Traduction Cycle Cellulaire et Développement, Station Biologique de Roscoff, Roscoff 29682 France