A Pin1/Mutant p53 Axis Promotes Aggressiveness in Breast Cancer

被引：279

作者：

Girardini, Javier E. ^{[1
,2
]}

Napoli, Marco ^{[1
,2
]}

Piazza, Silvano ^{[1
]}

Rustighi, Alessandra ^{[1
,2
]}

Marotta, Carolina ^{[1
,2
]}

Radaelli, Enrico ^{[3
,4
]}

Capaci, Valeria ^{[1
,2
]}

Jordan, Lee

Quinlan, Phil ^{[5
]}

Thompson, Alastair ^{[5
,6
]}

Mano, Miguel ^{[8
]}

Rosato, Antonio ^{[9
,10
]}

Crook, Tim ^{[5
]}

Scanziani, Eugenio ^{[3
,4
]}

Means, Anthony R. ^{[11
]}

Lozano, Guillermina ^{[7
]}

Schneider, Claudio ^{[1
,12
]}

Del Sal, Giannino ^{[1
,2
]}

机构：

[1] Lab Nazl CIB LNCIB, I-34149 Trieste, Italy

[2] Univ Trieste, Dipartimento Sci Vita, I-34127 Trieste, Italy

[3] Univ Milan, Dipartimento Patol Anim Igiene & Sanita Pubbl Vet, I-20139 Milan, Italy

[4] Fdn Filarete, Mouse & Anim Pathol Lab, I-20139 Milan, Italy

[5] Univ Dundee, Dundee Canc Ctr, Dundee DD1 9SY, Scotland

[6] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA

[7] Univ Texas MD Anderson Canc Ctr, Dept Canc Genet, Houston, TX 77030 USA

[8] ICGEB, I-34149 Trieste, Italy

[9] Univ Padua, Dipartimento Sci Oncol & Chirurg, I-35128 Padua, Italy

[10] Ist Oncol Veneto IRCCS, I-35128 Padua, Italy

[11] Duke Univ, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA

[12] Univ Udine, Dipartimento Sci & Tecnol Biomed, I-33100 Udine, Italy

来源：

CANCER CELL | 2011年 / 20卷 / 01期

关键词：

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

D O I：

10.1016/j.ccr.2011.06.004

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

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.

引用

页码：79 / 91

页数：13

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