{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T22:50:07Z","timestamp":1782600607259,"version":"3.54.5"},"reference-count":51,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["R15CA246419"],"award-info":[{"award-number":["R15CA246419"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Cancer cells often have defects in antiviral pathways, making them susceptible to oncolytic viruses like vesicular stomatitis virus (VSV). However, some cancer cells resist viral infection through the constitutive expression of interferon-stimulated genes. This study examined whether NF-\u03baB activation and NF-\u03baB-dependent antiviral signaling contribute to resistance to VSV infection in the PC3 cell line, derived from an aggressive metastatic prostate cancer (PrCa) tumor. We found that NF-\u03baB localized to the nucleus in VSV-infected PC3 cells, but not in the VSV-susceptible LNCaP PrCa cell line. Analysis of the upstream NF-\u03baB inhibitor I\u03baB-\u03b1 revealed higher levels of both total and phosphorylated I\u03baB-\u03b1 in PC3 cells compared to LNCaP cells, indicating constitutive activation of the NF-\u03baB pathway via an I\u03baB-\u03b1-dependent mechanism. Notably, VSV infection did not alter I\u03baB-\u03b1 phosphorylation in PC3 cells, suggesting that VSV may amplify NF-\u03baB signaling through an I\u03baB-\u03b1\u2013independent pathway. Furthermore, PC3 cells displayed elevated levels of the NF-\u03baB p65 protein subunit compared to LNCaP cells, with its phosphorylated form significantly increased upon VSV infection. These results from phosphorylation assays confirm that multiple steps in the NF-\u03baB pathway are differentially activated in PC3 and LNCaP cells. Finally, the expression of several NF-\u03baB-dependent cytokines and proinflammatory genes, including IL12 and IL6, was upregulated following VSV infection in PC3 cells, as compared to LNCaP cells. Collectively, these findings suggest that enhanced NF-\u03baB signaling may underlie the resistance of PC3 cells to VSV oncolysis, potentially offering new insights into therapeutic strategies targeting NF-\u03baB in resistant prostate cancers.<\/jats:p>","DOI":"10.3390\/v18010067","type":"journal-article","created":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T12:23:44Z","timestamp":1767356624000},"page":"67","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Constitutive NF-kB Activation Is Amplified by VSV in Aggressive PC3 Prostate Cancer Cells That Resist Viral Oncolysis"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-3891-3642","authenticated-orcid":false,"given":"Alaa A.","family":"Abdelmageed","sequence":"first","affiliation":[{"name":"Biomedical Genetics and Genomics Program, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA"},{"name":"Department of Biomedical Genetics, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-2370-9444","authenticated-orcid":false,"given":"Jack F.","family":"Smerczynski","sequence":"additional","affiliation":[{"name":"Gosnell School for Life Sciences, Rochester Institute of Technology, Rochester, NY 14623, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mukul","family":"Kandwal","sequence":"additional","affiliation":[{"name":"Gosnell School for Life Sciences, Rochester Institute of Technology, Rochester, NY 14623, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lute J.","family":"Douglas","sequence":"additional","affiliation":[{"name":"Gosnell School for Life Sciences, Rochester Institute of Technology, Rochester, NY 14623, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-4301-0305","authenticated-orcid":false,"given":"Tori L.","family":"Russell","sequence":"additional","affiliation":[{"name":"Gosnell School for Life Sciences, Rochester Institute of Technology, Rochester, NY 14623, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1236-1255","authenticated-orcid":false,"given":"Matthew C.","family":"Morris","sequence":"additional","affiliation":[{"name":"Rochester Regional Health Systems, Rochester, NY 14620, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7729-7920","authenticated-orcid":false,"given":"Stephen","family":"Dewhurst","sequence":"additional","affiliation":[{"name":"Department of Biomedical Genetics, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA"},{"name":"Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0515-8582","authenticated-orcid":false,"given":"Maureen C.","family":"Ferran","sequence":"additional","affiliation":[{"name":"Gosnell School for Life Sciences, Rochester Institute of Technology, Rochester, NY 14623, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1089\/vim.2004.17.516","article-title":"Vesicular stomatitis virus as an oncolytic vector","volume":"17","author":"Barber","year":"2004","journal-title":"Viral Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2529","DOI":"10.1099\/vir.0.046672-0","article-title":"Vesicular stomatitis virus as a flexible platform for oncolytic virotherapy against cancer","volume":"93","author":"Hastie","year":"2012","journal-title":"J. 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