ArticleExperimental & molecular medicine2024
Elevated expression of WSB2 degrades p53 and activates the IGFBP3-AKT-mTOR-dependent pathway to drive hepatocellular carcinoma.
Article in Experimental & molecular medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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19 citing papers in PubMed, 24 citations in OpenAlex.
- EGFR-dependent delivery of phosphorylated IGFBP3 by cancer stem cells drives chemotherapy resistance in colorectal cancer.Cell death & disease · 2026Article
- Comprehensive analysis to develop a stromal senescence-associated gene signature for predicting hepatocellular carcinoma.Translational cancer research · 2026Article
- Insulin-like growth factor binding protein-3 serves as a biomarker for resistance to enzalutamide in prostate cancer.Apoptosis : an international journal on programmed cell death · 2026Article
- Metabolic reprogramming in cancer: dysregulation of glucose, lipid, and amino acid pathways and therapeutic opportunities.Molecular biomedicine · 2026Review
- Comprehensive analysis and therapeutic implications of prognostic value of circadian rhythm genes in hepatocellular carcinoma.Journal of physiology and biochemistry · 2026Article
- Knockout of IGFBP3 improves alcohol-induced liver injury via Akt/GSK3β and TMEM219/caspase 8 pathways.Frontiers in physiology · 2026Article
- Recessive variants in WSB2 encoding a substrate receptor of E3 ubiquitin ligase underlie a neurodevelopmental syndrome.European journal of human genetics : EJHG · 2026Article
- Characterization and Phenolic Profiling of AnticandidalACS omega · 2025Article
- Molecular network of metabolic reprogramming and precision diagnosis and treatment of hepatocellular carcinoma.Biomarker research · 2025Review
- Elevated FBXO45 promotes TFG ubiquitination and drives lung metastasis of hepatocellular carcinoma.JHEP reports : innovation in hepatology · 2025Article
- Pan‑cancer analysis of the carcinogenic role of WSB2 in human tumors.Molecular medicine reports · 2025Article
- IGFBP3-mediated effects of an effective combination therapy on HCC.Scientific reports · 2025Article
- IGFBP3 modulation of tumor pathogenesis and cell signaling pathways (Review).Oncology letters · 2025Review
- Exploring the mechanism of Naringenin in the treatment of hepatocellular carcinoma based on mRNA sequencing and experimental validation.Scientific reports · 2025Article
- FTO-mediated mClinical and translational medicine · 2025Article
- Article
- Screening and regulatory mechanisms of biomarkers related to neddylation in laryngeal squamous cell carcinoma.Frontiers in molecular biosciences · 2025Article
- Knockout of onecut2 inhibits proliferation and promotes apoptosis of tumor cells through SKP2-mediated p53 acetylation in hepatocellular carcinoma.Cellular and molecular life sciences : CMLS · 2024Article
- Article
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dysregulation of wild-type p53 turnover is a key cause of hepatocellular carcinoma (HCC), yet its mechanism remains poorly understood. Here, we report that WD repeat and SOCS box containing protein 2 (WSB2), an E3 ubiquitin ligase, is an independent adverse prognostic factor in HCC patients. WSB2 drives HCC tumorigenesis and lung metastasis in vitro and in vivo. Mechanistically, WSB2 is a new p53 destabilizer that promotes K48-linked p53 polyubiquitination at the Lys291 and Lys292 sites in HCC cells, leading to p53 proteasomal degradation. Degradation of p53 causes IGFBP3-dependent AKT/mTOR signaling activation. Furthermore, WSB2 was found to bind to the p53 tetramerization domain via its SOCS box domain. Targeting mTOR with everolimus, an oral drug, significantly blocked WSB2-triggered HCC tumorigenesis and metastasis in vivo. In clinical samples, high expression of WSB2 was associated with low wild-type p53 expression and high p-mTOR expression. These findings demonstrate that WSB2 is overexpressed and degrades wild-type p53 and then activates the IGFBP3-AKT/mTOR axis, leading to HCC tumorigenesis and lung metastasis, which indicates that targeting mTOR could be a new therapeutic strategy for HCC patients with high WSB2 expression and wild-type p53.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.