{"entity": "publication", "iuid": "e66c55b4d83847ba8e3e8acaf07e6072", "timestamp": "2026-08-23T09:26:24.152Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/e66c55b4d83847ba8e3e8acaf07e6072.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/e66c55b4d83847ba8e3e8acaf07e6072"}}, "title": "GPX4 transcriptionally promotes liver cancer metastasis via GRHL3/PTEN/PI3K/AKT axis.", "authors": [{"family": "Pan", "given": "Ruogu", "initials": "R"}, {"family": "Zhao", "given": "Zhenjun", "initials": "Z"}, {"family": "Xu", "given": "Dongwei", "initials": "D"}, {"family": "Li", "given": "Chunlai", "initials": "C"}, {"family": "Xia", "given": "Qiang", "initials": "Q"}], "type": "journal article", "published": "2024-09-00", "journal": {"title": "Transl Res", "issn": "1878-1810", "volume": "271", "pages": "79-92", "issn-l": null}, "abstract": "Hepatocellular carcinoma (HCC) is among the most fatal types of malignancy, with a high prevalence of relapse and limited treatment options. As a critical regulator of ferroptosis and redox homeostasis, glutathione peroxidase 4 (GPX4) is commonly upregulated in HCC and is hypothesized to facilitate cancer metastasis, but this has not been fully explored in HCC. Here, we report that up-regulated GPX4 expression in HCC is strongly associated with tumor metastasis. FACS-based in vivo and in vitro analysis revealed that a cell subpopulation featuring lower cellular reactive oxygen species levels and ferroptosis resistance were involved in GPX4-mediated HCC metastasis. Mechanistically, GPX4 overexpressed in HCC tumor cells was enriched in the nucleus and transcriptionally silenced GRHL3 expression, thereby activating PTEN/PI3K/AKT signaling and promoting HCC metastasis. Functional studies demonstrated that GPX4 amino acids 110-145 are a binding site that interacts with the GRHL3 promoter. As AKT is a downstream target of GPX4, we combined the AKT inhibitor, AKT-IN3, with lenvatinib to effectively inhibit HCC tumor cell metastasis. Overall, these results indicate that the GPX4/GRHL3/PTEN/PI3K/AKT axis controls HCC cell metastasis and lenvatinib combined with AKT-IN3 represents a potential therapeutic strategy for patients with metastatic HCC.", "doi": "10.1016/j.trsl.2024.05.007", "pmid": "38797432", "labels": [], "xrefs": [{"db": "pii", "key": "S1931-5244(24)00107-5"}], "notes": [], "created": "2026-08-21T11:30:38.048Z", "modified": "2026-08-21T11:30:38.077Z"}