ArticleCell death & disease2020
Targeting the ERβ/Angiopoietin-2/Tie-2 signaling-mediated angiogenesis with the FDA-approved anti-estrogen Faslodex to increase the Sunitinib sensitivity in RCC.
Article in Cell death & disease, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 43 citations in OpenAlex.
- Mechanism of Shoutai Wan against recurrent spontaneous abortion: regulation of decidual vascular remodeling via ERβ-ANGPT2 signaling axis.Functional & integrative genomics · 2026Article
- VHL Suppresses Angiogenesis Through HIF-1a-Mediated Ang/Tie2/AMPK/VEGF Signaling Pathway in Tie-2 Expressed Macrophages (TEMs).Biochemical genetics · 2026Article
- Unveiling the role of ANGPT2 in esophageal cancer: A prognostic factor and potential oncogene.Oncology reports · 2026Article
- Insights into the mechanisms of drug resistance in renal cell carcinoma: from multi-omics perspective.International journal of surgery (London, England) · 2026Article
- ANGPT2 Drives Thyroid Cancer Progression Through PI3K/AKT Signaling and Correlates With Poor Prognosis and Immune Infiltration.World journal of otorhinolaryngology - head and neck surgery · 2026Article
- The Role of Estrogen Signaling Pathway and Targeted Therapy Exploration in Urological Tumors.International journal of biological sciences · 2026Review
- ERβ/circAHNAK Axis Inhibits USP10-FMR1 Deubiquitination to Prevent m⁶A-Mediated ADAM17 Decay and Promote Angiogenesis in Clear Cell Renal Cell Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Renal cell carcinoma organoids for precision medicine: bridging the gap between models and patients.Journal of translational medicine · 2025Review
- Unraveling the mechanisms of tricetin in renal cell carcinoma treatment through network pharmacology and experimental validation.Medical oncology (Northwood, London, England) · 2025Article
- Angiogenic and immune predictors of neoadjuvant axitinib response in renal cell carcinoma with venous tumour thrombus.Nature communications · 2025Article
- The correlation between serum sex hormone levels and clear cell renal cell carcinoma in male patients.Scientific reports · 2025Article
- ERβ-regulated circATP2B1/miR-204-3p/TWIST1 positive feedback loop facilitates epithelial to mesenchymal transition in clear cell renal cell carcinoma.Translational oncology · 2025Article
- Recent progress on tyrosine kinase inhibitors resistance in renal cell carcinoma: another brick in the wall?Cancer drug resistance (Alhambra, Calif.) · 2025Review
- Identification and Experimental Validation of Prognostic Signature and Peroxisome-Related Key Genes in Clear Cell Renal Cell Carcinoma.International journal of general medicine · 2025Article
- Gastric metastasis of renal cell carcinoma: features, mechanisms, and insights from existing literature.Frontiers in cell and developmental biology · 2025Review
- Specificity of endothelial cells in endothelial dysfunction of diabetic kidney disease and their crosstalk with neighboring cells: an updated review.Frontiers in endocrinology · 2025Review
- Serum angiopoietin-2/angiopoietin-1 ratio is associated with cardiovascular and all-cause mortality in peritoneal dialysis patients: a prospective cohort study.Renal failure · 2024Article
- Benzophenone-3 alters expression of genes encoding vascularization and epithelial-mesenchymal transition functions during Trp53-null mammary tumorigenesis.Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2024Article
- Improved therapy for clear cell renal cell carcinoma: beta-hydroxybutyrate and quercetin target hypoxia-induced angiogenesis and multidrug resistance.Molecular biology reports · 2024Article
- Identification and validation of shared gene signature of kidney renal clear cell carcinoma and COVID-19.PeerJ · 2024Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sunitinib has been used as the main therapy to treat the metastatic clear cell renal cell carcinoma (ccRCC) as it could function via suppressing the tumor growth and angiogenesis. Yet most ccRCC tumors may still regrow due to the development of sunitinib-resistance, and detailed mechanisms remain to be further investigated. The angiopoietin family includes angiopoietin-1 and angiopoietin-2 (ANGPT-1 and -2). It was reported that estradiol regulates expression of ANGPT-1, but not ANGPT-2, through estrogen receptor α (ERα) in an experimental stroke model. To date, there is no finding to link the E2/ER signal on regulating ANGPT-2. Our study is the first to explore (i) how estrogen receptor β (ERβ) can up-regulate ANGPT-2 in RCC cells, and (ii) how ERβ-increased ANGPT-2 can promote the HUVEC tube formation and reduce sunitinib sensitivity. Mechanistic studies revealed that ERβ could function via transcriptional regulation of the cytokine ANGPT-2 in the ccRCC cells. We found the up-regulated ANGPT-2 of RCC cells could then increase the Tie-2 phosphorylation to promote the angiogenesis and increase sunitinib treatment resistance of endothelial cells. In addition to the endothelial cell tube formation and aortic ring assay, preclinical studies with a mouse RCC model also confirmed the finding. Targeting this newly identified ERβ/ANGPT-2/Tie-2 signaling pathway with the FDA-approved anti-estrogen, Faslodex, may help in the development of a novel combined therapy with sunitinib to better suppress the ccRCC progression.
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