A Pin1/Mutant p53 Axis Promotes Aggressiveness in Breast Cancer

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

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    186 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)79-91
    Number of pages13
    JournalCancer Cell
    Volume20
    Issue number1
    DOIs
    Publication statusPublished - 12 Jul 2011

    Keywords

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

    Cite this

    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. (2011). A Pin1/Mutant p53 Axis Promotes Aggressiveness in Breast Cancer. Cancer Cell, 20(1), 79-91. https://doi.org/10.1016/j.ccr.2011.06.004