ArticleCancer communications (London, England)2021
Junction plakoglobin regulates and destabilizes HIF2α to inhibit tumorigenesis of renal cell carcinoma.
Article in Cancer communications (London, England), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 16 citations in OpenAlex.
- OTUD1 delays wound healing by regulating endothelial function and angiogenesis in diabetic mice.Journal of advanced research · 2026Article
- Suppression of ASNS expression by VHL-mediated ubiquitination hinders the progression of renal cell carcinoma through enhancing JUP expression and inhibiting PI3K-AKT and MAPK pathways.International journal of biological sciences · 2026Article
- The Role of Endoplasmic Reticulum Stress in Polycystic Ovary Syndrome and Exploration of Potential Therapeutic Targets.Reproductive sciences (Thousand Oaks, Calif.) · 2025Article
- Histone deacetylases and their inhibitors in kidney diseases.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Junction Plakoglobin - A Dual-Role Player in Cancer Biology.International journal of surgery (London, England) · 2025Review
- Multi-omics analysis unveils a four-gene prognostic signature in esophageal squamous carcinoma and the therapeutic potential of PKP1.BMC cancer · 2025Article
- Unraveling the role ofBiomolecules & biomedicine · 2025Article
- Mitophagy-related gene TRIP13 predicts prognosis and immune response and promotes proliferation and migrationFrontiers in pharmacology · 2025Article
- Article
- XAF1 promotes colorectal cancer metastasis via VCP-RNF114-JUP axis.The Journal of cell biology · 2024Article
- HIF2α Promotes Cancer Metastasis through TCF7L2-Dependent Fatty Acid Synthesis in ccRCC.Research (Washington, D.C.) · 2024Article
- Histone Deacetylase 1 Expression and Regulatory Network in Lung Adenocarcinoma Based on Data Mining and Implications for Targeted Treatment.Journal of oncology · 2023Article
- Proteomes of Residual Tumors in Curcumin-Treated Rats Reveal Changes in Microenvironment/Malignant Cell Crosstalk in a Highly Invasive Model of Mesothelioma.International journal of molecular sciences · 2022Article
- Junction plakoglobin regulates and destabilizes HIF2α to inhibit tumorigenesis of renal cell carcinoma.Cancer communications (London, England) · 2021Article
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Authors and funding
16 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIncreased hypoxia-inducible factor 2α (HIF2α) activation is a common event in clear cell renal cell carcinoma (ccRCC) progression. However, the function and underlying mechanism of HIF2α in ccRCC remains uninvestigated. We conducted this study to access the potential link between junction plakoglobin (JUP) and HIF2α in ccRCC.
methodsAffinity purification and mass spectrometry (AP-MS) screening, glutathione-s-transferase (GST) pull-down and co-immunoprecipitation (Co-IP) assays were performed to detect the interacting proteins of HIF2α. Quantitative PCR (qPCR) and Western blotting were used to detect the expression of JUP in human ccRCC samples. Luciferase reporter assays, chromatin immunoprecipitation (ChIP), cycloheximide chase assays, and ubiquitination assays were conducted to explore the regulation of JUP on the activity of HIF2α. Cell Counting Kit-8 (CCK-8) assays, colony formation assays, transwell assays, and xenograft tumor assays were performed to investigate the effect of JUP knockdown or overexpression on the tumorigenicity of renal cancer cells.
resultsWe identified JUP as a novel HIF2α-binding partner and revealed an important role of JUP in recruiting von Hippel-Lindau (VHL) and histone deacetylases 1/2 (HDAC1/2) to HIF2α to regulate its stability and transactivation. JUP knockdown promoted and overexpression suppressed the tumorigenicity of renal cell carcinoma in vitro and in vivo. Importantly, the low expression of JUP was found in clinical ccRCC samples and correlated with enhanced hypoxia scores and poor treatment outcomes.
conclusionTaken together, these data support a role of JUP in modulating HIF2α signaling during ccRCC progression and identify JUP as a potential therapeutic target.
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