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.
authors: Laboratorio Nazionale CIB, Trieste, Italy.
authors: Javier E
authors: JE
authors: Girardini
authors: Marco
authors: M
authors: Napoli
authors: Silvano
authors: S
authors: Piazza
authors: Alessandra
authors: A
authors: Rustighi
authors: Carolina
authors: C
authors: Marotta
authors: Enrico
authors: E
authors: Radaelli
authors: Valeria
authors: V
authors: Capaci
authors: Lee
authors: L
authors: Jordan
authors: Phil
authors: P
authors: Quinlan
authors: Alastair
authors: A
authors: Thompson
authors: Miguel
authors: M
authors: Mano
authors: Antonio
authors: A
authors: Rosato
authors: Tim
authors: T
authors: Crook
authors: Eugenio
authors: E
authors: Scanziani
authors: Anthony R
authors: AR
authors: Means
authors: Guillermina
authors: G
authors: Lozano
authors: Claudio
authors: C
authors: Schneider
authors: Giannino
authors: G
authors: Del Sal
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055879:Gene Knock-In Techniques; D006801:Humans; D051379:Mice; D008954:Models, Biological; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism*; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D009361:Neoplasm Invasiveness; D019696:Peptidylprolyl Isomerase / Q000378:metabolism*; D014158:Transcription, Genetic; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D050505:Mutant Proteins; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D016159:Tumor Suppressor Protein p53; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase; C000606850:Pin1 protein, mouse