Mutant p53 Attenuates the Anti-Tumorigenic Activity of Fibroblasts-Secreted Interferon Beta Shalom Madar Einav Harel Ido Goldstein Yan Stein Ira Kogan-Sakin Iris Kamer Hilla Solomon Elya Dekel Perry Tal Naomi Goldfinger Gilgi Friedlander Varda Rotter 10.1371/journal.pone.0061353 https://plos.figshare.com/articles/dataset/_Mutant_p53_Attenuates_the_Anti_Tumorigenic_Activity_of_Fibroblasts_Secreted_Interferon_Beta_/687847 <div><p>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.</p></div> 2013-04-22 02:10:47 genetics gene expression DNA transcription RNA stability Cancer genetics Gene networks Genetic mutation Genetics of disease immunology Immunologic subspecialties Tumor immunology Molecular cell biology Signal transduction Signaling in cellular processes Antiapoptotic signaling Signaling in selected disciplines Oncogenic signaling Clinical immunology oncology Cancers and neoplasms Lung and intrathoracic tumors Adenocarcinoma of the lung p53 attenuates anti-tumorigenic fibroblasts-secreted interferon