ArticleEBioMedicine2020
Cdh1-mediated Skp2 degradation by dioscin reprogrammes aerobic glycolysis and inhibits colorectal cancer cells growth.
Article in EBioMedicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 1 of them a synthesis that pooled it.
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Who cites it
51 citing papers in PubMed, 1 synthesis or guideline pooled it, 89 citations in OpenAlex.
- Natural products targeting glycolysis in cancer.Frontiers in pharmacology · 2022Pooled it
- Dioscin Reverses Drug Resistance via AKT/GSK3β-mediated P-gp Degradation and EMT Inhibition.Drug development research · 2026Article
- Dioscin suppresses tumorigenesis and overcomes radioresistance by promoting ubiquitination-mediated degradation of Mcl-1.Cancer gene therapy · 2026Article
- Curcumol Induces G1 Phase Arrest in SK-Hep-1 Cells by Targeting SKP2-Mediated p27 Degradation.Molecules (Basel, Switzerland) · 2026Article
- SKP2 in Cancer: From Molecular Regulation to Therapeutic Vulnerabilities and Translational Perspectives.Drug design, development and therapy · 2026Review
- Targeted protein degradation of Wnt/β-catenin signaling pathway: an effective strategy for cancer therapy.Journal of translational medicine · 2025Review
- Article
- Modulation of almonertinib resistance in non-small cell lung cancer by cancer-associated fibroblasts through HK2-mediated glycolysis and SKP2 signaling.Discover oncology · 2025Article
- Anticancer and Antioxidant Effects of Bioactive Peptides from Black Soldier Fly Larvae (Nutrients · 2025Article
- The anti-cancer activity of Dioscin: an update and future perspective.Medical oncology (Northwood, London, England) · 2025Review
- Metabolic Targets in CRC: The Emerging Role of Cytochrome P450 Inhibitors.Current pharmaceutical design · 2025Review
- The Role of HK2 in Tumorigenesis and Development: Potential for Targeted Therapy with Natural Products.International journal of medical sciences · 2025Review
- Inhibition of Dormant Lung Cancer Cell Reactivation byDrug design, development and therapy · 2025Article
- Impact and mechanism study of dioscin on biological characteristics of colorectal cancer cells.World journal of gastrointestinal oncology · 2024Article
- Natural Products and Derivatives Targeting Metabolic Reprogramming in Colorectal Cancer: A Comprehensive Review.Metabolites · 2024Review
- Suppression of Skp2 contributes to sepsis-induced acute lung injury by enhancing ferroptosis through the ubiquitination of SLC3A2.Cellular and molecular life sciences : CMLS · 2024Article
- The cross talk of ubiquitination and chemotherapy tolerance in colorectal cancer.Journal of cancer research and clinical oncology · 2024Review
- Targeting SMAD-Dependent Signaling: Considerations in Epithelial and Mesenchymal Solid Tumors.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Serum erythropoietin in acute ischemic stroke: preliminary findings.Scientific reports · 2024Article
- Dioscin inhibits non-small cell lung cancer cells and activates apoptosis by downregulation of Survivin.Journal of Cancer · 2024Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe F-box protein S-phase kinase-associated protein 2 (Skp2) is overexpressed and correlated with poor prognosis in human malignancies, including colorectal cancer (CRC).
methodsA natural product library was used for natural compound screening through glycolysis analysis. The expression of Skp2 in CRCs and the inhibitory effect of dioscin on glycolysis were examined through methods of immunoblot, immunofluorescence, immunohistochemical staining, anchorage-dependent and -independent growth assays, EdU incorporation assay, ubiquitination analysis, co-immunoprecipitation assay, CRISPR-Cas9-based gene knockout, and xenograft experiment.
findingsWe demonstrated that Skp2 was highly expressed in CRC tissues and cell lines. Knockout of Skp2 inhibited HK2 and glycolysis and decreased CRC cell growth in vitro and in vivo. We screened 88 commercially available natural products and found that dioscin, a natural steroid saponin derived from several plants, significantly inhibited glycolysis in CRC cells. Dioscin decreased the protein level of Skp2 by shortening the half-life of Skp2. Further study showed that dioscin attenuated Skp2 phosphorylation on S72 and promoted the interaction between Skp2 and Cdh1, which eventually enhanced Skp2 lysine 48 (K48)-linked polyubiquitination and degradation. Depletion of Cdh1 impaired dioscin-induced Skp2 reduction, rescued HK2 expression, and glycolysis in CRC cells. Finally, dioscin delayed the in vivo tumor growth, promoted Skp2 ubiquitination, and inhibited Skp2 expression in a mouse xenograft model.
interpretationThis study suggests that in addition to pharmacological inactivation of Skp2, enhancement of ubiquitination-dependent Skp2 turnover is a promising approach for cancer treatment.
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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.