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

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

241 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

Keywords

PROLYL-ISOMERASE PIN1
LI-FRAUMENI-SYNDROME
GAIN-OF-FUNCTION
MUTANT P53
MUTATION STATUS
MOUSE MODEL
CELL-CYCLE
EXPRESSION
INSTABILITY
REVEALS

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.ccr.2011.06.004

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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

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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.",

keywords = "PROLYL-ISOMERASE PIN1, LI-FRAUMENI-SYNDROME, GAIN-OF-FUNCTION, MUTANT P53, MUTATION STATUS, MOUSE MODEL, CELL-CYCLE, EXPRESSION, INSTABILITY, REVEALS",

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",

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

language = "English",

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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

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.

KW - PROLYL-ISOMERASE PIN1

KW - LI-FRAUMENI-SYNDROME

KW - GAIN-OF-FUNCTION

KW - MUTANT P53

KW - MUTATION STATUS

KW - MOUSE MODEL

KW - CELL-CYCLE

KW - EXPRESSION

KW - INSTABILITY

KW - REVEALS

U2 - 10.1016/j.ccr.2011.06.004

DO - 10.1016/j.ccr.2011.06.004

M3 - Article

C2 - 21741598

SN - 1535-6108

VL - 20

SP - 79

EP - 91

JO - Cancer Cell

JF - Cancer Cell

IS - 1

ER -

A Pin1/Mutant p53 Axis Promotes Aggressiveness in Breast Cancer

Abstract

Keywords

UN SDGs

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