A Pin1/Mutant p53 Axis Promotes Aggressiveness in Breast Cancer

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• 作者：Javier  ; E. Girardini¹ ; ² ; ¹² ; Marco Napoli¹ ; ² ; ¹² ; Silvano Piazza¹ ; Alessandra Rustighi¹ ; ² ; Carolina Marotta¹ ; ² ; Enrico Radaelli³ ; ⁴ ; Valeria Capaci¹ ; ² ; Lee Jordan⁵ ; Phil Quinlan⁵ ; Alastair Thompson⁵ ; ⁶ ; Miguel Mano⁸ ; Antonio Rosato⁹ ; Tim Crook⁵ ; Eugenio Scanziani³ ; ⁴ ; Anthony  ; R. Means¹⁰ ; Guillermina Lozano⁷ ; Claudio Schneider¹ ; ¹¹ ; Giannino Del  ; Sal¹ ; ² ; ^{delsal@lncib.it"" rel=""nofollow}
• 刊名：Cancer Cell
• 出版年：2011
• 出版时间：12 July 2011
• 年：2011
• 卷：20
• 期：1
• 页码：79-91
• 全文大小：1044 K

文摘

Summary

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.