Mutant p53 potentiates the oncogenic effects of insulin by inhibiting the tumor suppressor DAB2IP

Elena Valentino, Arianna Bellazzo, Giulio Di Minin, Daria Sicari, Mattia Apollonio, Giosuè Scognamiglio, Maurizio Di Bonito, Gerardo Botti, Giannino Del Sal, Licio Collavin

Research output: Contribution to journalArticlepeer-review


Obesity and type 2 diabetes are significant risk factors for malignancies, being associated with chronic inflammation and hyperinsulinemia. In this context, insulin can synergize with inflammation to promote proliferation, survival, and dissemination of cancer cells. Point mutation of p53 is a frequent event and a significant factor in cancer development and progression. Mutant p53 protein(s) (mutp53) can acquire oncogenic properties that increase metastasis, proliferation, and cell survival. We report that breast and prostate cancer cells with mutant p53 respond to insulin stimulation by increasing cell proliferation and invasivity, and that such a response depends on the presence of mutp53. Mechanistically, we find that mutp53 augments insulin-induced AKT1 activation by binding and inhibiting the tumor suppressor DAB2IP (DAB2-interacting protein) in the cytoplasm. This molecular axis reveals a specific gain of function for mutant p53 in the response to insulin stimulation, offering an additional perspective to understand the relationship between hyperinsulinemia and cancer evolution.

Original languageEnglish
Pages (from-to)7623-7628
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number29
Publication statusPublished - Jul 18 2017


  • AIP1
  • AKT
  • Hyperinsulinemia
  • Mutant p53
  • Obesity

ASJC Scopus subject areas

  • General


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