ArticleCancer gene therapy2025
FBXO22 promotes HCC angiogenesis and metastasis via RPS5/AKT/HIF-1α/VEGF-A signaling axis.
Article in Cancer gene therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- FXYD5 promotes the growth of glioblastoma by targeting the PI3K/AKT/ACSL4 signaling axis.Oncology reports · 2026Article
- New insights into the physiological, pathological and pharmacological roles of voltage‑gated potassium channel Kv10.1 in cancer (Review).International journal of oncology · 2026Review
- LARS promotes hepatocellular carcinoma progression via the PI3K/AKT/mTOR pathway and interaction with RPS5, and serves as a prognostic biomarker.Molecular medicine (Cambridge, Mass.) · 2026Article
- Radiomics predicts poorly differentiated hepatocellular carcinoma and uncovers ribosomal-immune dysregulation mechanism.iScience · 2026Article
- FBXO22 promotes hepatocellular carcinoma progression via paracrine myo‑inositol‑induced M2‑type polarization of macrophages.International journal of molecular medicine · 2026Article
- Mechanisms of lactylation modification in hepatocellular carcinoma treatment resistance.Gastroenterology report · 2026Review
- TMEM160 promotes hepatocellular carcinoma cell proliferation, invasion, and immune evasion by regulating the VEGFA/PI3K/AKT signaling axis.Frontiers in immunology · 2026Article
- The central regulator HIF-1α in digestive system pathologies: inflammation and cancer.Frontiers in immunology · 2026Review
- Article
- F-box proteins in cancer: from cancer cells to the tumor microenvironment.Cell communication and signaling : CCS · 2025Review
- FBXO42 promotes hepatocellular carcinoma progression via mediating p57Kip2 ubiquitination and degradation.European journal of medical research · 2025Article
- FBXO2 promotes hepatocellular carcinoma progression and sorafenib resistance by targeting USP49 for proteasomal degradation.Frontiers in immunology · 2025Article
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Authors and funding
8 authors.
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Abstract
The gene F-box only protein 22 (FBXO22) has been discovered to promote the development of liver cancer tumors. Nevertheless, there remains considerable ambiguity regarding the involvement of FBXO22 in the processes of angiogenesis and metastasis in hepatocellular carcinoma (HCC). Our study has confirmed a significant upregulation of FBXO22 expression in both HCC samples and cellular models. The increased level of FBXO22 correlates strongly with the number of tumors, presence of vascular invasion, and poor prognosis. Experimental investigations have shown that FBXO22 significantly enhances angiogenesis and metastasis of HCC both in vitro and in vivo. Mechanistically, FBXO22 interacts with and ubiquitinates 40S ribosomal protein S5 (RPS5) on Lys85, thereby promoting its K48-linked ubiquitin-mediated degradation in the cytoplasm. Following a decrease in the expression of RPS5, activation of downstream PI3K/AKT signaling pathway occurs, leading to elevated levels of HIF-1α and vascular endothelial growth factor A (VEGF-A). Our study has shown that FBXO22 facilitates HCC angiogenesis and metastasis via the RPS5/AKT/HIF-1α/VEGF-A signaling axis. Notably, inhibition of FBXO22 enhances the efficacy of Lenvatinib both in vitro and in vivo. Therefore, FBXO22 may present itself as a potential target for therapeutic intervention in the treatment of HCC.
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