ArticleCell death & disease2023
UBE2S interacting with TRIM21 mediates the K11-linked ubiquitination of LPP to promote the lymphatic metastasis of bladder cancer.
Article in Cell death & disease, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 42 citations in OpenAlex.
- CircARHGAP10 inhibits colorectal cancer cell proliferation, migration and invasion by governing the miR-29a-5p/LPP axis and regulating Wnt/β-catenin signaling pathway.Molecular and cellular biochemistry · 2026Article
- DIXDC1 Promotes Lymphatic Metastasis and Resistance to Cuproptosis in Bladder Cancer Through Mediating DLAT.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Article
- circZNF148 Drives Glucose Metabolism Reprogramming to Enhance Metastasis and Immune Evasion via HK1 Stabilization in Triple-Negative Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Oncogenic LPP facilitates focal adhesion maturation in response to mechanical tension and regulates the Hippo signaling.Oncogene · 2026Article
- Targeting TPX2-dependent lineage plasticity by CDK4/6 inhibition reverses therapy resistance in neuroendocrine bladder carcinoma.Cell reports. Medicine · 2026Article
- Nuclear hexokinase 2 couples hyperglycemia to MYC-driven glycolytic and stemness programs in bladder cancer.Cell death & disease · 2026Article
- Macrophage TRIM21 Inhibition Ameliorates Murine Acute Pancreatitis via PHB2-Mediated Mitochondrial Stabilization.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Miniature and versatile genome regulation TnpB-ωRNA toolkits facilitate cancer immunotherapy.Nature communications · 2026Article
- FomA-Containing Outer Membrane Vesicles of Fusobacterium Nucleatum Facilitate Bladder Cancer Lymphatic Metastasis via IL-6-Dependent M2b Macrophage Polarization.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Post-translational modifications: Principal regulators of bladder cancer.Molecular biology reports · 2026Review
- TRIM21 and OTUD6A orchestrate AKT K27-linked atypical ubiquitination to modulate cancer chemoresistance.Nature structural & molecular biology · 2026Article
- USP7 promotes chemotherapy resistance and DNA damage response through stabilizing and deubiquitinating KDM4A in bladder cancer.Cell death & disease · 2025Article
- Targeting the SMAD3/CISD2 axis suppresses bladder cancer progression by promoting ferroptosis in mesenchymal-like bladder cancer cells.Cell death & disease · 2025Article
- Ubiquitin-conjugating enzyme E2S serves as a prognostic marker for skin cutaneous melanoma.Translational cancer research · 2025Article
- TRIM21 as a potential prognostic biomarker and therapeutic target affects the growth of pancreatic cancer.Discover oncology · 2025Article
- KDM1A-driven RNF81 downregulation promotes gastric cancer progression via KLF4 destabilization.Oncogene · 2025Article
- The ETS transcription factor GABPA inhibits bladder cancer aggressiveness by repressing extracellular matrix deposition and mechanotransduction signaling.Cell death & disease · 2025Article
- Review
- METTL21A promotes hepatocellular carcinoma progression via methylating and stabilizing BAG3.NPJ precision oncology · 2025Article
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lymphatic metastasis is the most common pattern of bladder cancer (BCa) metastasis and has an extremely poor prognosis. Emerging evidence shows that ubiquitination plays crucial roles in various processes of tumors, including tumorigenesis and progression. However, the molecular mechanisms underlying the roles of ubiquitination in the lymphatic metastasis of BCa are largely unknown. In the present study, through bioinformatics analysis and validation in tissue samples, we found that the ubiquitin-conjugating E2 enzyme UBE2S was positively correlated with the lymphatic metastasis status, high tumor stage, histological grade, and poor prognosis of BCa patients. Functional assays showed that UBE2S promoted BCa cell migration and invasion in vitro, as well as lymphatic metastasis in vivo. Mechanistically, UBE2S interacted with tripartite motif containing 21 (TRIM21) and jointly induced the ubiquitination of lipoma preferred partner (LPP) via K11-linked polyubiquitination but not K48- or K63-linked polyubiquitination. Moreover, LPP silencing rescued the anti-metastatic phenotypes and inhibited the epithelial-mesenchymal transition of BCa cells after UBE2S knockdown. Finally, targeting UBE2S with cephalomannine distinctly inhibited the progression of BCa in cell lines and human BCa-derived organoids in vitro, as well as in a lymphatic metastasis model in vivo, without significant toxicity. In conclusion, our study reveals that UBE2S, by interacting with TRIM21, degrades LPP through K11-linked ubiquitination to promote the lymphatic metastasis of BCa, suggesting that UBE2S represents a potent and promising therapeutic target for metastatic BCa.
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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.