{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T13:50:40Z","timestamp":1787061040435,"version":"build-2736575974"},"reference-count":35,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T00:00:00Z","timestamp":1775692800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>The incidence of hepatocellular carcinoma (HCC) is increasing each year, with challenges such as increasing drug resistance and a high post-treatment recurrence rate. Therefore, investigating the novel pathogenic mechanisms is warranted. In this study, we investigated novel molecular mechanisms that affect HCC progression. Immunofluorescence analysis, immunohistochemical staining, and immunoblotting were performed to assess elevated IGF-1R expression in HCC cells. The EdU incorporation and colony formation assays revealed that IGF-1R promotes HCC cell proliferation. Furthermore, wound healing and Transwell migration assays revealed that IGF-1R phosphorylation enhances the migration of HCC cells. In addition, JC-1 apoptosis assays revealed that IGF-1R inhibits HCC cell apoptosis. Immunoblotting was performed to assess the protein phosphorylation level of Akt\/GSK-3\u03b2 downstream of IGF1\/IGF-1R to explore the molecular mechanism. IGF-1R expression was significantly increased in HCC cells, and ligand-induced phosphorylation promoted HCC cell proliferation and migration and inhibited apoptosis. Additional studies revealed that the activation of IGF-1R phosphorylation promotes epithelial\u2013mesenchymal transition in HCC cells by increasing the phosphorylation levels of Akt and GSK-3\u03b2. Collectively, our study findings suggest that IGF-1\/IGF-1R promotes HCC progression by activating the Akt\/GSK-3\u03b2 pathway.<\/jats:p>","DOI":"10.1371\/journal.pone.0346926","type":"journal-article","created":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T17:33:01Z","timestamp":1775755981000},"page":"e0346926","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["IGF1\/IGF-1R promotes hepatocellular carcinoma progression by activating the Akt\/GSK-3\u03b2 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