ArticleThe Journal of clinical investigation2024
UBE2C-induced crosstalk between mono- and polyubiquitination of SNAT2 promotes lymphatic metastasis in bladder cancer.
Article in The Journal of clinical investigation, 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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Who cites it
19 citing papers in PubMed.
- UBE2C promotes pancreatic cancer progression through PI3K/Akt/mTOR signaling pathway.Cell cycle (Georgetown, Tex.) · 2026Article
- Cancer-Associated Fibroblasts Promote Glucose Metabolic Reprogramming and Progression of Triple-Negative Breast Cancer via Exosomal circFAD104-Mediated Intercellular Communication.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Article
- CRISPR Screen Reveals Pathways and Factors Driving Tyrosine Kinase Inhibitor Resistance in Hepatocellular Carcinoma.Cancer medicine · 2026Article
- Decoding the crosstalk between ubiquitination and other post-translational modifications in cancer immunity: from mechanisms to clinical prospects.NPJ precision oncology · 2026Review
- Pancancer Fine-Mapping of Mutational Intolerance Identifies CHEK1 as an Immunosuppressive Driver in Lung Adenocarcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Identification of key genes as diagnostic biomarkers for lung adenocarcinoma using bioinformatics and machine learning.Discover oncology · 2026Article
- Connexin43 Deficiency Leads to Ventricular Arrhythmias by Reprogramming Proline Metabolism.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Endocytic Adaptor Proteins in Vascular Diseases: Critical Role of Intracellular Trafficking in Regulating Pathobiology of Vascular Disorders.Cardiology discovery · 2026Review
- Post-translational modifications: Principal regulators of bladder cancer.Molecular biology reports · 2026Review
- Harnessing PDX and PDX 2.0: the next-generation paradigm for precision oncology and translational breakthroughs.Molecular cancer · 2026Review
- Halorotetin B, A Novel Terpenoid Compound Derived from Marine Ascidian, Suppresses Tumor Growth by Targeting the Cell Cycle Regulator UBE2C.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- KDM5C-regulated SIX5 promotes glioblastoma progression through transcriptional activation of UBE2C and enhancement of the Warburg effect.Frontiers in immunology · 2026Article
- Ubiquitin-conjugating Enzymes in Cancer.International journal of biological sciences · 2026Review
- PTM-Related Signatures Predict Lymph Node Metastasis and Shape Microenvironment in Hepatocellular Carcinoma: A Single-Cell and Bulk Integrated Analysis.Journal of hepatocellular carcinoma · 2026Article
- Exploring targeted therapies against RFPL3 for non-small cell lung cancer with lymph node metastasis.Discover oncology · 2025Article
- [NIP7 upregulates the expression of ubiquitin-conjugating enzyme E2 C to promote tumor growth in anaplastic thyroid cancer].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2025Article
- Regulation of placental development and function by ubiquitination.Molecular medicine (Cambridge, Mass.) · 2025Review
- UBE2N as a novel prognostic and therapeutic biomarker of lung adenocarcinoma.Frontiers in immunology · 2025Article
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Authors and funding
10 authors.
Funding
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Abstract
Ubiquitination plays an essential role in protein stability, subcellular localization, and interactions. Crosstalk between different types of ubiquitination results in distinct biological outcomes for proteins. However, the role of ubiquitination-related crosstalk in lymph node (LN) metastasis and the key regulatory factors controlling this process have not been determined. Using high-throughput sequencing, we found that ubiquitin-conjugating enzyme E2 C (UBE2C) was overexpressed in bladder cancer (BCa) and was strongly associated with an unfavorable prognosis. Overexpression of UBE2C increased BCa lymphangiogenesis and promoted LN metastasis both in vitro and in vivo. Mechanistically, UBE2C mediated sodium-coupled neutral amino acid transporter 2 (SNAT2) monoubiquitination at lysine 59 to inhibit K63-linked polyubiquitination at lysine 33 of SNAT2. Crosstalk between monoubiquitination and K63-linked polyubiquitination increased SNAT2 membrane protein levels by suppressing epsin 1-mediated (EPN1-mediated) endocytosis. SNAT2 facilitated glutamine uptake and metabolism to promote VEGFC secretion, ultimately leading to lymphangiogenesis and LN metastasis in patients with BCa. Importantly, inhibition of UBE2C significantly attenuated BCa lymphangiogenesis in a patient-derived xenograft model. Our results reveal the mechanism by which UBE2C mediates crosstalk between the monoubiquitination and K63-linked polyubiquitination of SNAT2 to promote BCa metastasis and identify UBE2C as a promising target for treating LN-metastatic BCa.
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