ArticleOncogene2021
A novel UBE2T inhibitor suppresses Wnt/β-catenin signaling hyperactivation and gastric cancer progression by blocking RACK1 ubiquitination.
Article in Oncogene, 2021. 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 71 papers, 1 of them a synthesis that pooled it.
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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
71 citing papers in PubMed, 1 synthesis or guideline pooled it, 103 citations in OpenAlex.
- Prognostic and clinicopathological role of RACK1 for cancer patients: a systematic review and meta-analysis.PeerJ · 2023Pooled it
- Protein modification systems as cancer biomarkers and therapeutic targets.Precision clinical medicine · 2026Review
- UBE2T-Driven p53 Degradation Rewires Glycolysis to Orchestrate Lactylation-Mediated CAFs Activation and ECM Deposition in Pancreatic Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- 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
- Ubiquitin-conjugating Enzymes in Cancer.International journal of biological sciences · 2026Review
- Role and mechanistic study of long non-coding RNA maternally expressed gene 3 in gastric cancer (Review).Oncology letters · 2025Review
- A moonlighting function of tumoral interleukin-1β precursor promotes metastasis via RACK1-mediated actin remodeling.Nature communications · 2025Article
- Smurf1 promotes gastric cancer progression by regulating Axin2-dependent Wnt signaling pathway.Scientific reports · 2025Article
- UBE2T promotes epithelial-mesenchymal transition and motility in oral cancer cells via induction of IL-6 expression.Oncology letters · 2025Article
- OTUD1 deficiency attenuates myocardial ischemia/reperfusion induced cardiomyocyte apoptosis by regulating RACK1 phosphorylation.Acta pharmacologica Sinica · 2025Article
- UBE2T-Mediated HP1α Ubiquitination Enhances Nucleolar Function and Promotes the Progression of IDH1/TP53-Mutant Glioma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Spatial Analysis of Hereditary Diffuse Gastric Cancer Reveals Indolent Phenotype of Signet Ring Cell Precursors.Molecular cancer research : MCR · 2025Article
- Wnt signaling in cancer: from biomarkers to targeted therapies and clinical translation.Molecular cancer · 2025Review
- Article
- Research Progress on the Role of Zinc Finger Protein in Colorectal Cancer.Cancer reports (Hoboken, N.J.) · 2025Review
- KRASCell reports. Medicine · 2025Article
- Rack1 promotes breast cancer stemness properties and tumorigenesis through the E2F1-SOX2 axis.Cancer cell international · 2025Article
- UBE2T/CDC42/CD276 signaling axis mediates brain metastasis of triple-negative breast cancer via lysosomal autophagy.Journal for immunotherapy of cancer · 2025Article
- LRP11 facilitates lipid metabolism and malignancy in hepatocellular carcinoma by stabilizing RACK1 through USP5 regulation.Molecular medicine (Cambridge, Mass.) · 2025Article
- SHP2 promotes the epithelial-mesenchymal transition in triple negative breast cancer cells by regulating β-catenin.Journal of cancer research and clinical oncology · 2025Article
11 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
17 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dysregulation of the Wnt/β-catenin signaling pathway is critically involved in gastric cancer (GC) progression. However, current Wnt pathway inhibitors being studied in preclinical or clinical settings for other cancers such as colorectal and pancreatic cancers are either too cytotoxic or insufficiently efficacious for GC. Thus, we screened new potent targets from β-catenin destruction complex associated with GC progression from clinical samples, and found that scaffolding protein RACK1 deficiency plays a significant role in GC progression, but not APC, AXIN, and GSK3β. Then, we identified its upstream regulator UBE2T which promotes GC progression via hyperactivating the Wnt/β-catenin signaling pathway through the ubiquitination and degradation of RACK1 at the lysine K172, K225, and K257 residues independent of an E3 ligase. Indeed, UBE2T protein level is negatively associated with prognosis in GC patients, suggesting that UBE2T is a promising target for GC therapy. Furthermore, we identified a novel UBE2T inhibitor, M435-1279, and suggested that M435-1279 acts inhibit the Wnt/β-catenin signaling pathway hyperactivation through blocking UBE2T-mediated degradation of RACK1, resulting in suppression of GC progression with lower cytotoxicity in the meantime. Overall, we found that increased UBE2T levels promote GC progression via the ubiquitination of RACK1 and identified a novel potent inhibitor providing a balance between growth inhibition and cytotoxicity as well, which offer a new opportunity for the specific GC patients with aberrant Wnt/β-catenin signaling.
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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.