A Pin1/Mutant p53 Axis Promotes Aggressiveness in Breast Cancer

Javier E. Girardini, Marco Napoli, Silvano Piazza, Alessandra Rustighi, Carolina Marotta, Enrico Radaelli, Valeria Capaci, Lee Jordan, Phil Quinlan, Alastair Thompson, Miguel Mano, Antonio Rosato, Tim Crook, Eugenio Scanziani, Anthony R. Means, Guillermina Lozano, Claudio Schneider, Giannino Del Sal

Research output: Contribution to journalArticlepeer-review

Abstract

TP53 missense mutations dramatically influence tumor progression, however, their mechanism of action is still poorly understood. Here we demonstrate the fundamental role of the prolyl isomerase Pin1 in mutant p53 oncogenic functions. Pin1 enhances tumorigenesis in a Li-Fraumeni mouse model and cooperates with mutant p53 in Ras-dependent transformation. In breast cancer cells, Pin1 promotes mutant p53 dependent inhibition of the antimetastatic factor p63 and induction of a mutant p53 transcriptional program to increase aggressiveness. Furthermore, we identified a transcriptional signature associated with poor prognosis in breast cancer and, in a cohort of patients, Pin1 overexpression influenced the prognostic value of p53 mutation. These results define a Pin1/mutant p53 axis that conveys oncogenic signals to promote aggressiveness in human cancers.

Original languageEnglish
Pages (from-to)79-91
Number of pages13
JournalCancer Cell
Volume20
Issue number1
DOIs
Publication statusPublished - Jul 12 2011

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Oncology

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