{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T23:11:59Z","timestamp":1779923519241,"version":"3.53.1"},"reference-count":64,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,4,17]],"date-time":"2020-04-17T00:00:00Z","timestamp":1587081600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Direct acting antivirals (DAAs) revolutionized the therapy of chronic hepatitis C infection. However, unexpected high recurrence rates of hepatocellular carcinoma (HCC) after DAA treatment became an issue in patients with advanced cirrhosis and fibrosis. In this study, we aimed to investigate an impact of DAA treatment on the molecular changes related to HCC development and progression in hepatoma cell lines and primary human hepatocytes. We found that treatment with sofosbuvir (SOF), a backbone of DAA therapy, caused an increase in EGFR expression and phosphorylation. As a result, enhanced translocation of EGFR into the nucleus and transactivation of factors associated with cell cycle progression, B-MYB and Cyclin D1, was detected. Serine\/threonine kinase profiling identified additional pathways, especially the MAPK pathway, also activated during SOF treatment. Importantly, the blocking of EGFR kinase activity by erlotinib during SOF treatment prevented all downstream events. Altogether, our findings suggest that SOF may have an impact on pathological processes in the liver via the induction of EGFR signaling. Notably, zidovudine, another nucleoside analogue, exerted a similar cell phenotype, suggesting that the observed effects may be induced by additional members of this drug class.<\/jats:p>","DOI":"10.3390\/cells9041003","type":"journal-article","created":{"date-parts":[[2020,4,21]],"date-time":"2020-04-21T05:48:52Z","timestamp":1587448132000},"page":"1003","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Sofosbuvir Activates EGFR-Dependent Pathways in Hepatoma Cells with Implications for Liver-Related Pathological Processes"],"prefix":"10.3390","volume":"9","author":[{"given":"Denisa","family":"Bojkova","sequence":"first","affiliation":[{"name":"Institute of Virology, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany"},{"name":"Institute of Medical Virology, University Hospital, Goethe University Frankfurt am Main, 60590 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Westhaus","sequence":"additional","affiliation":[{"name":"Institute of Virology, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany"},{"name":"Institute of Medical Virology, University Hospital, Goethe University Frankfurt am Main, 60590 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3048-6366","authenticated-orcid":false,"given":"Rui","family":"Costa","sequence":"additional","affiliation":[{"name":"Institute of Virology, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lejla","family":"Timmer","sequence":"additional","affiliation":[{"name":"Institute of Virology, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nora","family":"Funkenberg","sequence":"additional","affiliation":[{"name":"Institute of Virology, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marek","family":"Korencak","sequence":"additional","affiliation":[{"name":"Institute for HIV research, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hendrik","family":"Streeck","sequence":"additional","affiliation":[{"name":"Institute for HIV research, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Vondran","sequence":"additional","affiliation":[{"name":"Clinic for General, Abdominal and Transplant Surgery, Hannover Medical School, 30625 Hannover, Germany"},{"name":"German Center for Infection Research (DZIF), 45147 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7125-3246","authenticated-orcid":false,"given":"Ruth","family":"Broering","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Heinrichs","sequence":"additional","affiliation":[{"name":"Institute for Transfusion Medicine, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl S","family":"Lang","sequence":"additional","affiliation":[{"name":"Institute of Immunology, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1802-7565","authenticated-orcid":false,"given":"Sandra","family":"Ciesek","sequence":"additional","affiliation":[{"name":"Institute of Virology, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany"},{"name":"Institute of Medical Virology, University Hospital, Goethe University Frankfurt am Main, 60590 Frankfurt, Germany"},{"name":"German Center for Infection Research (DZIF), 45147 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,17]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2017). 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