TY - JOUR
T1 - A Pin1/Mutant p53 Axis Promotes Aggressiveness in Breast Cancer
AU - Girardini, Javier E.
AU - Napoli, Marco
AU - Piazza, Silvano
AU - Rustighi, Alessandra
AU - Marotta, Carolina
AU - Radaelli, Enrico
AU - Capaci, Valeria
AU - Jordan, Lee
AU - Quinlan, Phil
AU - Thompson, Alastair
AU - Mano, Miguel
AU - Rosato, Antonio
AU - Crook, Tim
AU - Scanziani, Eugenio
AU - Means, Anthony R.
AU - Lozano, Guillermina
AU - Schneider, Claudio
AU - Del Sal, Giannino
N1 - Funding Information:
We acknowledge A. Di Leo, S. Piccolo, F. Mantovani for helpful discussion and reading the manuscript; S. Gustincich for advice in microarray; M. Giacca for access to the ICGEB facilities; E. Tagliafico for support in bioinformatic analysis; S. Piccolo for providing Dicer cDNA and T. Katagiri for providing DEPDC1 cDNA. M.N. is a fellow of the Fondazione Italiana per la Ricerca sul Cancro (FIRC). This work was supported by grants from the Associazione Italiana per la Ricerca sul Cancro (AIRC) and AIRC Special Program Molecular Clinical Oncology “5 per mille,” Regione Friuli-Venezia Giulia, Italian University and Research Ministerium (Cofin MIUR) to G.D.S; grant R01 CA082845 from NIH to A.R.M.; and the European Community Sixth Framework Programme funding (Mutant p53, LSHC-CT-2004-502983) to G.D.S. This publication reflects the authors' views and not necessarily those of the European Community. The European Community is not liable for any use that may be made of the information contained herein.
PY - 2011/7/12
Y1 - 2011/7/12
N2 - 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.
AB - 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.
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U2 - 10.1016/j.ccr.2011.06.004
DO - 10.1016/j.ccr.2011.06.004
M3 - Article
C2 - 21741598
AN - SCOPUS:79960039752
SN - 1535-6108
VL - 20
SP - 79
EP - 91
JO - Cancer cell
JF - Cancer cell
IS - 1
ER -