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

doi:10.1016/j.ccr.2011.06.004

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^*

^*Corresponding author for this work

Cardiovascular Sciences

Research output: Contribution to journal › Article › peer-review

239 Citations (Scopus)

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 language	English
Pages (from-to)	79-91
Number of pages	13
Journal	CANCER CELL
Volume	20
Issue number	1
DOIs	https://doi.org/10.1016/j.ccr.2011.06.004
Publication status	Published - 12 Jul 2011

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Girardini, J. E., Napoli, M., Piazza, S., Rustighi, A., Marotta, C., Radaelli, E., Capaci, V., Jordan, L., Quinlan, P., Thompson, A., Mano, M., Rosato, A., Crook, T., Scanziani, E., Means, A. R., Lozano, G., Schneider, C., & Del Sal, G. (2011). A Pin1/Mutant p53 Axis Promotes Aggressiveness in Breast Cancer. CANCER CELL, 20(1), 79-91. https://doi.org/10.1016/j.ccr.2011.06.004

@article{d3fc5cb987324229b95bcbb614c6f5b2,

title = "A Pin1/Mutant p53 Axis Promotes Aggressiveness in Breast Cancer",

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.",

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

note = "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. ",

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doi = "10.1016/j.ccr.2011.06.004",

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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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DO - 10.1016/j.ccr.2011.06.004

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SN - 1535-6108

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EP - 91

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IS - 1

ER -

A Pin1/Mutant p53 Axis Promotes Aggressiveness in Breast Cancer

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