ArticleThe Journal of experimental medicine2012
SCF(β-TRCP) suppresses angiogenesis and thyroid cancer cell migration by promoting ubiquitination and destruction of VEGF receptor 2.
Article in The Journal of experimental medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 64 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
64 citing papers in PubMed, 93 citations in OpenAlex.
- UBE2M-mediated neddylation modification stabilizes VEGFR2 to delay pulmonary vascular endothelial cell senescence.Cell death & disease · 2026Article
- Gene Expression Profiles Associated with Molecular Subtypes and Pathological Response to Neoadjuvant Treatment in Surgical Breast Cancer.International journal of molecular sciences · 2026Article
- F-box proteins in cancer: from cancer cells to the tumor microenvironment.Cell communication and signaling : CCS · 2025Review
- Vascular endothelial growth factor signaling in health and disease: from molecular mechanisms to therapeutic perspectives.Signal transduction and targeted therapy · 2025Review
- D-mannose suppresses the angiogenesis and progression of colorectal cancer.Acta biochimica et biophysica Sinica · 2025Article
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- New insights into the role of ubiquitination in angiogenesis (Review).International journal of molecular medicine · 2025Review
- Association between genetic mutations in lung adenocarcinoma and adult body mass index: a retrospective cohort study.Frontiers in oncology · 2025Article
- Polymorphisms in circadian rhythm genes and the risk of differentiated thyroid cancer.Frontiers in genetics · 2025Article
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- ESM1 Interacts with c-Met to Promote Gastric Cancer Peritoneal Metastasis by Inducing Angiogenesis.Cancers · 2023Article
- CRISPR screening identifies the deubiquitylase ATXN3 as a PD-L1-positive regulator for tumor immune evasion.The Journal of clinical investigation · 2023Article
- The Tyrosine Kinase Inhibitor Lenvatinib Inhibits Anaplastic Thyroid Carcinoma Growth by Targeting Pericytes in the Tumor Microenvironment.Thyroid : official journal of the American Thyroid Association · 2023Article
- The E2 ubiquitin-conjugating enzymes UBE2D1 and UBE2D2 regulate VEGFR2 dynamics and endothelial function.Journal of cell science · 2023Article
- Emerging role of ubiquitination/deubiquitination modification of PD-1/PD-L1 in cancer immunotherapy.Genes & diseases · 2023Review
- Protein post-translational modifications in the regulation of cancer hallmarks.Cancer gene therapy · 2023Review
- Exploiting E3 ubiquitin ligases to reeducate the tumor microenvironment for cancer therapy.Experimental hematology & oncology · 2023Review
- Casein kinase 1α mediates eryptosis: a review.Apoptosis : an international journal on programmed cell death · 2023Review
- Article
- Revealing β-TrCP activity dynamics in live cells with a genetically encoded biosensor.Nature communications · 2022Article
4 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
17 authors at 9 institutions in 2 countries.
Funding
Abstract
The incidence of human papillary thyroid cancer (PTC) is increasing and an aggressive subtype of this disease is resistant to treatment with vascular endothelial growth factor receptor 2 (VEGFR2) inhibitor. VEGFR2 promotes angiogenesis by triggering endothelial cell proliferation and migration. However, the molecular mechanisms governing VEGFR2 stability in vivo remain unknown. Additionally, whether VEGFR2 influences PTC cell migration is not clear. We show that the ubiquitin E3 ligase SCF(β-TRCP) promotes ubiquitination and destruction of VEGFR2 in a casein kinase I (CKI)-dependent manner. β-TRCP knockdown or CKI inhibition causes accumulation of VEGFR2, resulting in increased activity of signaling pathways downstream of VEGFR2. β-TRCP-depleted endothelial cells exhibit enhanced migration and angiogenesis in vitro. Furthermore, β-TRCP knockdown increased angiogenesis and vessel branching in zebrafish. Importantly, we found an inverse correlation between β-TRCP protein levels and angiogenesis in PTC. We also show that β-TRCP inhibits cell migration and decreases sensitivity to the VEGFR2 inhibitor sorafenib in poorly differentiated PTC cells. These results provide a new biomarker that may aid a rational use of tyrosine kinase inhibitors to treat refractory PTC.
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Registered trials
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.