{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T19:23:16Z","timestamp":1787772196051,"version":"build-2784847793"},"reference-count":78,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,2,25]],"date-time":"2022-02-25T00:00:00Z","timestamp":1645747200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Hepatocellular carcinoma (HCC) is one of the most frequent and essentially incurable cancers in its advanced stages. The tyrosine kinase inhibitor Sorafenib (Sfb) remains the globally accepted treatment for advanced HCC. However, the extent of its therapeutic benefit is limited. Sfb exerts antitumor activity through its cytotoxic, anti-proliferative and pro-apoptotic roles in HCC cells. To better understand the molecular mechanisms underlying these effects, we used RNA sequencing to generate comprehensive transcriptome profiles of HepG2 and SNU423, hepatoblastoma- (HB) and HCC-derived cell lines, respectively, following a Sfb treatment at a pharmacological dose. This resulted in similar alterations of gene expression in both cell lines. Genes functionally related to membrane trafficking, stress-responsible and unfolded protein responses, circadian clock and activation of apoptosis were predominantly upregulated, while genes involved in cell growth and cycle, DNA replication and repair, ribosome biogenesis, translation initiation and proteostasis were downregulated. Our results suggest that Sfb causes primary effects on cellular stress that lead to upregulation of selective responses to compensate for its negative effect and restore homeostasis. No significant differences were found specifically affecting each cell line, indicating the robustness of the Sfb mechanism of action despite the heterogeneity of liver cancer. We discuss our results on terms of providing rationalization for possible strategies to improve Sfb clinical outcomes.<\/jats:p>","DOI":"10.3390\/cancers14051204","type":"journal-article","created":{"date-parts":[[2022,2,25]],"date-time":"2022-02-25T10:00:40Z","timestamp":1645783240000},"page":"1204","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Broad Transcriptomic Impact of Sorafenib and Its Relation to the Antitumoral Properties in Liver Cancer Cells"],"prefix":"10.3390","volume":"14","author":[{"given":"Laura","family":"Contreras","sequence":"first","affiliation":[{"name":"Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Roc\u00edo\/CSIC\/Universidad de Sevilla, E-41013 Seville, Spain"},{"name":"Departamento de Gen\u00e9tica, Facultad de Biolog\u00eda, Universidad de Sevilla, E-41012 Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4430-077X","authenticated-orcid":false,"given":"Alfonso","family":"Rodr\u00edguez-Gil","sequence":"additional","affiliation":[{"name":"Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Roc\u00edo\/CSIC\/Universidad de Sevilla, E-41013 Seville, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer (CIBERONC), E-28029 Madrid, Spain"},{"name":"Departamento de Fisiolog\u00eda M\u00e9dica y Biof\u00edsica, Universidad de Sevilla, E-41009 Sevilla, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6744-1121","authenticated-orcid":false,"given":"Jordi","family":"Muntan\u00e9","sequence":"additional","affiliation":[{"name":"Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Roc\u00edo\/CSIC\/Universidad de Sevilla, E-41013 Seville, Spain"},{"name":"Departamento de Fisiolog\u00eda M\u00e9dica y Biof\u00edsica, Universidad de Sevilla, E-41009 Sevilla, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBEREHD), E-28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5870-659X","authenticated-orcid":false,"given":"Jes\u00fas","family":"de la Cruz","sequence":"additional","affiliation":[{"name":"Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Roc\u00edo\/CSIC\/Universidad de Sevilla, E-41013 Seville, Spain"},{"name":"Departamento de Gen\u00e9tica, Facultad de Biolog\u00eda, Universidad de Sevilla, E-41012 Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"394","DOI":"10.3322\/caac.21492","article-title":"Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"68","author":"Bray","year":"2018","journal-title":"CA Cancer J. 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