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