title: Mutant p53 reprograms TNF signaling in cancer cells through interaction with the tumor suppressor DAB2IP.
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.
authors.affiliation: Laboratorio Nazionale CIB (LNCIB), AREA Science Park, 34149 Trieste, Italy.
authors.forename: Giulio
authors.initials: G
authors.lastname: Di Minin
authors.affiliation: Laboratorio Nazionale CIB (LNCIB), AREA Science Park, 34149 Trieste, Italy; Dip. Scienze della Vita, Università degli Studi di Trieste, 34127 Trieste, Italy.
authors.forename: Arianna
authors.initials: A
authors.lastname: Bellazzo
authors.affiliation: Laboratorio Nazionale CIB (LNCIB), AREA Science Park, 34149 Trieste, Italy; Dip. Scienze della Vita, Università degli Studi di Trieste, 34127 Trieste, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Dal Ferro
authors.affiliation: International Centre for Genetic Engineering and Biotechnology (ICGEB), AREA Science Park, 34149 Trieste, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Chiaruttini
authors.affiliation: Center for Genome Research, Dip. Scienze della Vita, Università degli Studi di Modena e Reggio Emilia, 41121 Modena, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Nuzzo
authors.affiliation: Center for Genome Research, Dip. Scienze della Vita, Università degli Studi di Modena e Reggio Emilia, 41121 Modena, Italy.
authors.forename: Silvio
authors.initials: S
authors.lastname: Bicciato
authors.affiliation: Laboratorio Nazionale CIB (LNCIB), AREA Science Park, 34149 Trieste, Italy.
authors.forename: Silvano
authors.initials: S
authors.lastname: Piazza
authors.affiliation: Dip. Scienze della Vita, Università degli Studi di Trieste, 34127 Trieste, Italy.
authors.forename: Damiano
authors.initials: D
authors.lastname: Rami
authors.affiliation: Dip. Scienze della Vita, Università degli Studi di Trieste, 34127 Trieste, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Bulla
authors.affiliation: Dip. Scienze Chirurgiche Oncologiche e Gastroenterologiche, Università degli Studi di Padova, 35128 Padova, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Sommaggio
authors.affiliation: Dip. Scienze Chirurgiche Oncologiche e Gastroenterologiche, Università degli Studi di Padova, 35128 Padova, Italy; Istituto Oncologico Veneto IOV-IRCCS, 35128 Padova, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Rosato
authors.affiliation: Laboratorio Nazionale CIB (LNCIB), AREA Science Park, 34149 Trieste, Italy; Dip. Scienze della Vita, Università degli Studi di Trieste, 34127 Trieste, Italy.
authors.forename: Giannino
authors.initials: G
authors.lastname: Del Sal
authors.affiliation: Laboratorio Nazionale CIB (LNCIB), AREA Science Park, 34149 Trieste, Italy; Dip. Scienze della Vita, Università degli Studi di Trieste, 34127 Trieste, Italy. Electronic address: collavin@lncib.it.
authors.forename: Licio
authors.initials: L
authors.lastname: Collavin
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D003593:Cytoplasm / Q000378:metabolism; D005260:Female; D045325:HCT116 Cells; D006801:Humans; D008207:Lymphatic Metastasis; D008325:Mammary Neoplasms, Experimental; D051379:Mice; D016513:Mice, SCID; D020125:Mutation, Missense; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism*; D020703:ras GTPase-Activating Proteins / Q000378:metabolism*
chemical_list: D014409:Tumor Necrosis Factor-alpha; D016159:Tumor Suppressor Protein p53; D020703:ras GTPase-Activating Proteins