Mutant p53 Reprograms TNF Signaling in Cancer Cells through Interaction with the Tumor Suppressor DAB2IP

Giulio Di Minin, Arianna Bellazzo, Marco DalFerro, Giulia Chiaruttini, Simona Nuzzo, Silvio Bicciato, Silvano Piazza, Damiano Rami, Roberta Bulla, Roberta Sommaggio, Antonio Rosato, Giannino DelSal, Licio Collavin

Research output: Contribution to journalArticlepeer-review

Abstract

Inflammation is a significant factor in cancer development, and a molecular understanding of the parameters dictating the impact of inflammation on cancers could significantly improve treatment. The tumor suppressor p53 is frequently mutated in cancer, and p53 missense mutants (mutp53) can acquire oncogenic properties. We report that cancer cells with mutp53 respond to inflammatory cytokines increasing their invasive behavior. Notably, this action is coupled to expression of chemokines that can expose the tumor to host immunity, potentially affecting response to therapy. Mechanistically, mutp53 fuels NF-κB activation while it dampens activation of ASK1/JNK by TNFα, and this action depends on mutp53 binding and inhibiting the tumor suppressor DAB2IP in the cytoplasm. Interfering with such interaction reduced aggressiveness of cancer cells in xenografts. This interaction is an unexplored mechanism by which mutant p53 can influence tumor evolution, with implications for our understanding of the complex role of inflammation in cancer.

Original languageEnglish
Pages (from-to)617-629
Number of pages13
JournalMolecular Cell
Volume56
Issue number5
DOIs
Publication statusPublished - Dec 4 2014

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology
  • Medicine(all)

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