ArticleCell death & disease2021
The interplay of UBE2T and Mule in regulating Wnt/β-catenin activation to promote hepatocellular carcinoma progression.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 34 citations in OpenAlex.
- The UBE2/E2 ubiquitin-conjugating enzyme family at the interface of tumor biology and antitumor immunity: mechanisms, biomarkers, and therapeutic opportunities.Frontiers in immunology · 2026Review
- Post-Translational Modifications of Histones and Non-Histones in Liver Disease and Traditional Chinese Medicine Treatment: A Narrative Review.Pharmacogenomics and personalized medicine · 2026Review
- Ubiquitin-conjugating Enzymes in Cancer.International journal of biological sciences · 2026Review
- PANoptosis in hepatocellular carcinoma: Underlying mechanisms.World journal of hepatology · 2025Review
- UBE2T promotes epithelial-mesenchymal transition and motility in oral cancer cells via induction of IL-6 expression.Oncology letters · 2025Article
- Molecular subtyping combined with multiomics analysis to study correlation between TACE refractoriness and tumor stemness in hepatocellular carcinoma.Discover oncology · 2025Article
- UBE2S: A novel driver of HIF-1alpha-induced metabolic reprogramming in hepatocellular carcinoma: Editorial on "UBE2S promotes glycolysis in hepatocellular carcinoma by enhancing E3 enzyme-independent polyubiquitination of VHL".Clinical and molecular hepatology · 2025Article
- Navigating the Molecular Signaling: Deciphering Cancer Stem Cell Self-Renewal Pathways.International journal of molecular and cellular medicine · 2025Review
- Unraveling the Role of Ubiquitin-Conjugating Enzyme UBE2T in Tumorigenesis: A Comprehensive Review.Cells · 2024Review
- The role of ubiquitin-conjugating enzyme in the process of spermatogenesis.Reproductive biology and endocrinology : RB&E · 2024Review
- Role and therapeutic potential of E3s in the tumor microenvironment of hepatocellular carcinoma.Frontiers in immunology · 2024Review
- [Deubiquitinating enzyme MINDY1 is an independent risk factor for the maintenance of stemness and poor prognosis in liver cancer cells].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2023Article
- Article
- Diverse roles of UBE2T in cancer (Review).Oncology reports · 2023Article
- UBE2T promotes glioblastoma malignancy through ubiquitination-mediated degradation of RPL6.Cancer science · 2023Article
- Regulation of apoptosis by ubiquitination in liver cancer.American journal of cancer research · 2023Review
- Pathogenesis and Current Treatment Strategies of Hepatocellular Carcinoma.Biomedicines · 2022Review
- Pan-cancer analysis of UBE2T with a focus on prognostic and immunological roles in lung adenocarcinoma.Respiratory research · 2022Article
- Wnt/β-Catenin Signaling as a Driver of Stemness and Metabolic Reprogramming in Hepatocellular Carcinoma.Cancers · 2022Review
- UBE2T/STAT3 Signaling Promotes the Proliferation and Tumorigenesis in Retinoblastoma.Investigative ophthalmology & visual science · 2022Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Emerging evidence indicates the role of cancer stem cells (CSCs) in tumor relapse and therapeutic resistance in patients with hepatocellular carcinoma (HCC). To identify novel targets against liver CSCs, an integrative analysis of publicly available datasets involving HCC clinical and stemness-related data was employed to select genes that play crucial roles in HCC via regulation of liver CSCs. We revealed an enrichment of an interstrand cross-link repair pathway, in which ubiquitin-conjugating enzyme E2 T (UBE2T) was the most significantly upregulated. Consistently, our data showed that UBE2T was upregulated in enriched liver CSC populations. Clinically, UBE2T overexpression in HCC was further confirmed at mRNA and protein levels and was correlated with advanced tumor stage and poor patient survival. UBE2T was found to be critically involved in the regulation of liver CSCs, as evidenced by increases in self-renewal, drug resistance, tumorigenicity, and metastasis abilities. Mule, an E3 ubiquitin ligase, was identified to be the direct protein binding partner of UBE2T. Rather than the canonical role of acting as a mediator to transfer ubiquitin to E3 ligases, UBE2T is surprisingly able to physically bind and regulate the protein expression of Mule via ubiquitination. Mule was found to directly degrade β-catenin protein, and UBE2T was found to mediate liver CSC functions through direct regulation of Mule-mediated β-catenin degradation; this effect was abolished when the E2 activity of UBE2T was impaired. In conclusion, we revealed a novel UBE2T/Mule/β-catenin signaling cascade that is involved in the regulation of liver CSCs, which provides an attractive potential therapeutic target for HCC.
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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.