{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T16:06:24Z","timestamp":1774541184042,"version":"3.50.1"},"reference-count":76,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T00:00:00Z","timestamp":1774483200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Krieger Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>The mitochondrial anti-viral signaling protein, MAVS, is a central regulator of innate anti-viral immunity. Recently, we demonstrated that MAVS is overexpressed in cancer, where its downregulation resulted in reduced cell proliferation and the expression and nuclear translocation of proteins associated with transcriptional regulation and inflammation. In this study, we demonstrate that CRISPR\/Cas9-mediated MAVS depletion in PC-3 prostate cancer cells suppresses proliferation, disrupts immune evasion, and alters the tumor microenvironment. Proteomic profiling of the MAVS-KO cells by LC-MS\/MS revealed changes in the expression of proteins associated with immunity, cell signaling, mitochondrial function, metabolism, protein synthesis and degradation, and epigenetic regulation. In contrast to MAVS-expressing cells, MAVS-KO cells implanted subcutaneously in mice formed very small tumors. This inhibited tumor growth was linked to reduced proliferation, and enhanced apoptosis, as indicated by strong TUNEL staining and elevated activated caspase-3. Importantly, the small \u201ctumors\u201d derived from MAVS-KO cells displayed a distinct morphology: diminished cancer stem-cell populations, an altered tumor microenvironment and inflammatory response, increased immune cell infiltration, and reduced PD-L1 expression. Together, these findings establish MAVS as a key mediator of cancer-cell survival, inflammation, and immune regulation, and, thus, its upregulation in tumors makes it a potential anti-cancer target.<\/jats:p>","DOI":"10.3390\/biom16040501","type":"journal-article","created":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T15:10:24Z","timestamp":1774537824000},"page":"501","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["MAVS as a Key Regulator of Tumor Proliferation, Survival, the Tumor Microenvironment, and Immunity"],"prefix":"10.3390","volume":"16","author":[{"given":"Sweta","family":"Trishna","sequence":"first","affiliation":[{"name":"Department of Life Sciences, Ben-Gurion University of the Negev, Beer Sheva 84105, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0833-8407","authenticated-orcid":false,"given":"Anna","family":"Shteinfer-Kuzmine","sequence":"additional","affiliation":[{"name":"National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer Sheva 84105, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6030-5816","authenticated-orcid":false,"given":"Vered","family":"Chalifa-Caspi","sequence":"additional","affiliation":[{"name":"Ilse Katz Institute for Nanoscale Science and Technology, Ben-Gurion University of the Negev, Beer Sheva 84105, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6756-4340","authenticated-orcid":false,"given":"Varda","family":"Shoshan-Barmatz","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, Ben-Gurion University of the Negev, Beer Sheva 84105, Israel"},{"name":"National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer Sheva 84105, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1038\/s41577-022-00760-x","article-title":"Mitochondrial control of inflammation","volume":"23","author":"Marchi","year":"2023","journal-title":"Nat. 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