ArticleThe Journal of clinical investigation2021
Epsins 1 and 2 promote NEMO linear ubiquitination via LUBAC to drive breast cancer development.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 35 citations in OpenAlex.
- CircSPARC promotes esophageal squamous cell carcinoma through an HNRNPC-EPN2 splicing axis that activates Wnt/β-Catenin signaling.Molecular cancer · 2026Article
- Endocytic Adaptor Proteins in Vascular Diseases: Critical Role of Intracellular Trafficking in Regulating Pathobiology of Vascular Disorders.Cardiology discovery · 2026Review
- Immunogenomic diversity of triple-negative breast cancers in obese and non-obese black and white women.NPJ breast cancer · 2025Article
- Novel Biomarkers for Lymph Node Metastasis and Prognosis of Bladder Cancer by Bioinformatics Analysis.ACS omega · 2025Article
- Tob negatively regulates NF-κB activation in breast cancer through its association with the TNF receptor complex.Cancer gene therapy · 2025Article
- Review
- Epsin3 promotes non-small cell lung cancer progression via modulating EGFR stability.Cell & bioscience · 2025Article
- Ubiquitination Enzymes in Cancer, Cancer Immune Evasion, and Potential Therapeutic Opportunities.Cells · 2025Review
- FAM105B Promotes Hepatocellular Carcinoma Progression and Metastasis by Activating the PI3K/AKT/MTOR Signaling Pathway and Inducing Epithelial-Mesenchymal Transition.Journal of hepatocellular carcinoma · 2025Article
- Deciphering Key Regulatory Roles of Linear Ubiquitination in Cell Fate Determination and Disease.Research (Washington, D.C.) · 2025Review
- Ubiquitination and deubiquitination in cancer: from mechanisms to novel therapeutic approaches.Molecular cancer · 2024Review
- Mechanisms underlying linear ubiquitination and implications in tumorigenesis and drug discovery.Cell communication and signaling : CCS · 2023Review
- Peptidase inhibitor (PI16) impairs bladder cancer metastasis by inhibiting NF-κB activation via disrupting multiple-site ubiquitination of NEMO.Cellular & molecular biology letters · 2023Article
- Article
- Repositioning linifanib as a potent anti-necroptosis agent for sepsis.Cell death discovery · 2023Article
- Regulation of apoptosis by ubiquitination in liver cancer.American journal of cancer research · 2023Review
- The resurrection of RIP kinase 1 as an early cell death checkpoint regulator-a potential target for therapy in the necroptosis era.Experimental & molecular medicine · 2022Review
- Roles of ubiquitination in the crosstalk between tumors and the tumor microenvironment (Review).International journal of oncology · 2022Review
- Tumor-intrinsic and immune modulatory roles of receptor-interacting protein kinases.Trends in biochemical sciences · 2022Review
- Emerging Roles of Non-proteolytic Ubiquitination in Tumorigenesis.Frontiers in cell and developmental biology · 2022Review
Corrections and comments
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Authors and funding
21 authors at 5 institutions in 1 country.
Funding
Abstract
Estrogen receptor-negative (ER-negative) breast cancer is thought to be more malignant and devastating than ER-positive breast cancer. ER-negative breast cancer exhibits elevated NF-κB activity, but how this abnormally high NF-κB activity is maintained is poorly understood. The importance of linear ubiquitination, which is generated by the linear ubiquitin chain assembly complex (LUBAC), is increasingly appreciated in NF-κB signaling, which regulates cell activation and death. Here, we showed that epsin proteins, a family of ubiquitin-binding endocytic adaptors, interacted with LUBAC via its ubiquitin-interacting motif and bound LUBAC's bona fide substrate NEMO via its N-terminal homolog (ENTH) domain. Furthermore, epsins promoted NF-κB essential modulator (NEMO) linear ubiquitination and served as scaffolds for recruiting other components of the IκB kinase (IKK) complex, resulting in the heightened IKK activation and sustained NF-κB signaling essential for the development of ER-negative breast cancer. Heightened epsin levels in ER-negative human breast cancer are associated with poor relapse-free survival. We showed that transgenic and pharmacological approaches eliminating epsins potently impeded breast cancer development in both spontaneous and patient-derived xenograft breast cancer mouse models. Our findings established the pivotal role epsins played in promoting breast cancer. Thus, targeting epsins may represent a strategy to restrain NF-κB signaling and provide an important perspective into ER-negative breast cancer treatment.
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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.