Mutant p53 enhances nuclear factor κB activation by tumor necrosis factor α in cancer cells

Lilach Weisz, Alexander Damalas, Michalis Liontos, Panagiotis Karakaidos, Giulia Fontemaggi, Revital Maor-Aloni, Marina Kalis, Massimo Levrero, Sabrina Strano, Vassilis G. Gorgoulis, Varda Rotter, Giovanni Blandino, Moshe Oren

Research output: Contribution to journalArticlepeer-review

Abstract

Mutations in the p53 tumor suppressor are very frequent in human cancer. Often, such mutations lead to the constitutive overproduction of mutant p53 proteins, which may exert a cancer-promoting gain of function. We now report that cancer-associated mutant p53 can augment the induction of nuclear factor κB (NFκB) transcriptional activity in response to the cytokine tumor necrosis factor α (TNFα). Conversely, down-regulation of endogenous mutant p53 sensitizes cancer cells to the apoptotic effects of TNFα. Analysis of human head and neck tumors and lung tumors reveals a close correlation between the presence of abundant mutant p53 proteins and the constitutive activation of NFκB. Together, these findings suggest that p53 mutations may promote cancer progression by augmenting NFκB activation in the context of chronic inflammation.

Original languageEnglish
Pages (from-to)2396-2401
Number of pages6
JournalCancer Research
Volume67
Issue number6
DOIs
Publication statusPublished - Mar 15 2007

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Fingerprint Dive into the research topics of 'Mutant p53 enhances nuclear factor κB activation by tumor necrosis factor α in cancer cells'. Together they form a unique fingerprint.

Cite this