ArticleMolecular cancer2022
Targeting E2 ubiquitin-conjugating enzyme UbcH5c by small molecule inhibitor suppresses pancreatic cancer growth and metastasis.
Article in Molecular cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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33 citing papers in PubMed, 44 citations in OpenAlex.
- Identification and characterization of five anti-mitotic sesquiterpene lactones fromPharmaceutical biology · 2026Article
- Transcriptomic profiling reveals autophagy-associated programs and prognostic biomarkers in anoikis-resistant pancreatic cancer cells.BMC cancer · 2026Article
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- Erianin facilitates pyroptosis in endometrial cancer via targeting m6A reader YTHDF1.Chinese medicine · 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
- Morusin Suppresses Pancreatic Cancer Cell Proliferation and Migration by Targeting SLC6A12 to Inhibit NF-κB and β-catenin Signaling Pathways.Recent patents on anti-cancer drug discovery · 2026Article
- UBE2W promotes pancreatic cancer progression through regulating K63-linked ubiquitination of p53.American journal of cancer research · 2026Article
- Cul5: immune cell function and therapeutic potential.Frontiers in immunology · 2026Review
- Ubiquitin-conjugating Enzymes in Cancer.International journal of biological sciences · 2026Review
- Versatile roles of inositol hexakisphosphate in the ubiquitin-proteasome system.Essays in biochemistry · 2025Review
- Post-Translational Modifications: Key "Regulators" of Pancreatic Cancer Malignant Phenotype-Advances in Mechanisms and Targeted Therapies.Biomedicines · 2025Review
- Inhibition of integrin α3 suppresses gastric cancer progression via STAT3-mediated regulation of SLC1A5-dependent glutamine uptake.Journal of gastroenterology · 2025Article
- IFN-γ-driven UBE2D3 upregulation impairs antigen presentation pathways and anti-tumor immunity in pancreatic cancer.Nature communications · 2025Article
- Integrated scRNA-seq and transcriptome analyses uncover the effects of UBE2H on the immune microenvironment regulation in pancreatic cancer.Cancer cell international · 2025Article
- Targeting the Ubiquitin-Proteasome System for Cancer.MedComm · 2025Review
- Novel Cyano-Artemisinin Dimer ZQJ29 Targets PARP1 to Induce Ferroptosis in Pancreatic Cancer Treatment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Ubiquitin-conjugating enzyme UBE2N modulates proteostasis in immunoproteasome-positive acute myeloid leukemia.The Journal of clinical investigation · 2025Article
- Ubiquitination Enzymes in Cancer, Cancer Immune Evasion, and Potential Therapeutic Opportunities.Cells · 2025Review
- Macranthoside B Suppresses the Growth of Adenocarcinoma of Esophagogastric Junction by Regulating Iron Homeostasis and Ferroptosis through NRF2 Inhibition.Current cancer drug targets · 2025Article
- Eupalinolide B inhibits periodontitis development by targeting ubiquitin conjugating enzyme UBE2D3.MedComm · 2025Article
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPancreatic cancer is one of the most lethal cancers worldwide. The IAPs function as E3 ubiquitin ligases and contribute to pancreatic cancer initiation, progression, and metastasis. Although IAP-targeted therapies have been developed and shown anticancer efficacy in preclinical settings, none of them has been approved yet.
methodsTranscriptome data from public datasets were used to analyze the correlation of IAPs and E2s, and the biological function of E2 UbcH5c in pancreatic cancer. A structure-based virtual screen was used to identify UbcH5c inhibitor, and surface plasmon resonance analysis and cellular thermal shift assays were employed to evaluate the binding affinity. The anticancer activities were demonstrated through in vitro and in vivo assays, while the related mechanisms were explored through transcriptomic and proteomic analyses and confirmed by western blot, immunofluorescence, and qRT-PCR.
resultsUbcH5c is positively correlated with the expression of IAPs in pancreatic cancer. We further found that UbcH5c is overexpressed and associated with a poor prognosis in pancreatic cancer. We identified a small-molecule UbcH5c inhibitor, termed DHPO, which directly bound to UbcH5c protein. DHPO inhibited cell viability and colony formation, induced apoptosis, and suppressed migration and invasion of pancreatic cancer cells in vitro. The compound inhibited UbcH5c-mediated IκBα degradation and NF-κB activation, which is critical for its anticancer activity. Furthermore, DHPO suppressed the tumor growth and metastasis in two orthotopic pancreatic tumor mouse models.
conclusionsThese results indicated that inhibiting UbcH5c is a novel and effective strategy for treating pancreatic cancer and DHPO represents a new class of UbcH5c inhibitor and may be further developed as an anti-pancreatic cancer therapeutic agent.
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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.