title: Mutant p53 attenuates the anti-tumorigenic activity of fibroblasts-secreted interferon beta.
abstract: Mutations in the p53 tumor suppressor protein are highly frequent in tumors and often endow cells with tumorigenic capacities. We sought to examine a possible role for mutant p53 in the cross-talk between cancer cells and their surrounding stroma, which is a crucial factor affecting tumor outcome. Here we present a novel model which enables individual monitoring of the response of cancer cells and stromal cells (fibroblasts) to co-culturing. We found that fibroblasts elicit the interferon beta (IFNβ) pathway when in contact with cancer cells, thereby inhibiting their migration. Mutant p53 in the tumor was able to alleviate this response via SOCS1 mediated inhibition of STAT1 phosphorylation. IFNβ on the other hand, reduced mutant p53 RNA levels by restricting its RNA stabilizer, WIG1. These data underscore mutant p53 oncogenic properties in the context of the tumor microenvironment and suggest that mutant p53 positive cancer patients might benefit from IFNβ treatment.
authors: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
authors: Shalom
authors: S
authors: Madar
authors: Einav
authors: E
authors: Harel
authors: Ido
authors: I
authors: Goldstein
authors: Yan
authors: Y
authors: Stein
authors: Ira
authors: I
authors: Kogan-Sakin
authors: Iris
authors: I
authors: Kamer
authors: Hilla
authors: H
authors: Solomon
authors: Elya
authors: E
authors: Dekel
authors: Perry
authors: P
authors: Tal
authors: Naomi
authors: N
authors: Goldfinger
authors: Gilgi
authors: G
authors: Friedlander
authors: Varda
authors: V
authors: Rotter
mesh_terms: D002352:Carrier Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D018920:Coculture Techniques; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D016899:Interferon-beta / Q000378:metabolism*; D008175:Lung Neoplasms; D009154:Mutation; D009687:Nuclear Proteins / Q000378:metabolism; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D020871:RNA Stability; D016601:RNA-Binding Proteins; D050794:STAT1 Transcription Factor / Q000378:metabolism; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism; D019139:Tumor Escape; D059016:Tumor Microenvironment; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D002352:Carrier Proteins; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; C108944:SOCS1 protein, human; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C436503:ZMAT3 protein, human; D016899:Interferon-beta
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