IBR   13079
INSTITUTO DE BIOLOGIA MOLECULAR Y CELULAR DE ROSARIO
Unidad Ejecutora - UE
artículos
Título:
A Pin1/Mutant p53 Axis Promotes Aggressiveness in Breast Cancer
Autor/es:
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.
Revista:
CANCER CELL
Editorial:
CELL PRESS
Referencias:
Año: 2011 vol. 20 p. 79 - 91
ISSN:
1535-6108
Resumen:
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.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.