ArticleThe Journal of clinical investigation2021
Glucose deprivation-induced aberrant FUT1-mediated fucosylation drives cancer stemness in hepatocellular carcinoma.
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 59 papers.
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Who cites it
59 citing papers in PubMed, 108 citations in OpenAlex.
- Ferroptosis regulatory networks as therapeutic sensitizers in combination therapy for hepatocellular carcinoma (Review).Oncology letters · 2026Review
- Liver cancer derived high core fucosylation sEV elict malignancy by activating PI3K/AKT signaling pathway.Cell communication and signaling : CCS · 2026Article
- L-Fucose: a dietary sugar with multifaceted potential in the biology and therapy of cancer.Nature reviews. Cancer · 2026Review
- A Unique Intercellular Feedforward Loop From HK1 to TGF-β1 Promotes the Progression of Hepatocellular Carcinoma.Journal of extracellular vesicles · 2026Article
- Lysophosphatidic acid-induced Arf6-driven macropinocytosis of CD147International journal of biological sciences · 2026Article
- Nutrient Restriction Improves the Therapeutic Efficacy of Sorafenib by Inducing Ferroptosis via the NRF2/HO-1/GPX4 Pathway in Hepatocellular Carcinoma.Journal of hepatocellular carcinoma · 2026Article
- FUT3 mediated GRP78 fucosylation promotes colorectal cancer survival and proliferation under glucose restriction via PERK/ATF4/STC2 axis.NPJ precision oncology · 2025Article
- Structure, function, and implications of fucosyltransferases in health and disease.Nature communications · 2025Review
- Fucosylation in digestive inflammatory diseases and cancers: From mechanical studies to clinical translation.Genes & diseases · 2025Review
- Targeting mitochondrial translation and OXPHOS in high-grade serous ovarian carcinoma eliminates stem-like cells.Cell death & disease · 2025Article
- Combined downregulation of TGF-β1 and GRP78 is responsible for overcoming acquired sorafenib resistance, which is initiated by rewiring the cell surface CD44-GRP78-IGF-1R signaling circuit.Cancer gene therapy · 2025Article
- Sugar symphony: glycosylation in cancer metabolism and stemness.Trends in cell biology · 2025Review
- Cancer ATF4-mediated CD58 endocytosis impairs anti-tumor immunity and immunotherapy.Journal of translational medicine · 2025Article
- Comprehensive Multi-Omics Analysis Identifies FUT1 as a Prognostic and Therapeutic Biomarker Across Pan-Cancer.International journal of medical sciences · 2025Article
- Angiogenesis and Immunosuppressive Niche in Hepatocellular Carcinoma: Reshaping Vascular - Immune Axis to Potentiate antiPD - 1/PD - L1 Therapy.Cancer management and research · 2025Review
- Development of a Starvation Response-Based Model and Its Application in Prognostic Assessment of Liver Hepatocellular Carcinoma.Mediators of inflammation · 2025Article
- CD147 at the crossroads of glycoprotein networks, metabolic reprogramming, and metastatic progression.Frontiers in immunology · 2025Review
- An Overview of In Vitro Models of Alcohol-Related Hepatocellular Carcinoma.Cancer medicine · 2025Review
- F-type lectins: Structural and functional aspects, and potential biomedical applications.BBA advances · 2025Article
- Deciphering the cell surface glyco-code: a promising perspective on unveiling the vulnerability of cancer stem cells.Cancer biology & medicine · 2024Article
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Rapidly growing tumors often experience hypoxia and nutrient (e.g., glucose) deficiency because of poor vascularization. Tumor cells respond to the cytotoxic effects of such stresses by inducing molecular adaptations that promote clonal selection of a more malignant tumor-initiating cell phenotype, especially in the innermost tumor regions. Here, we report a regulatory mechanism involving fucosylation by which glucose restriction promotes cancer stemness to drive drug resistance and tumor recurrence. Using hepatocellular carcinoma (HCC) as a model, we showed that restricted glucose availability enhanced the PERK/eIF2α/ATF4 signaling axis to drive fucosyltransferase 1 (FUT1) transcription via direct binding of ATF4 to the FUT1 promoter. FUT1 overexpression is a poor prognostic indicator for HCC. FUT1 inhibition could mitigate tumor initiation, self-renewal, and drug resistance. Mechanistically, we demonstrated that CD147, ICAM-1, EGFR, and EPHA2 are glycoprotein targets of FUT1, in which such fucosylation would consequently converge on deregulated AKT/mTOR/4EBP1 signaling to drive cancer stemness. Treatment with an α-(1,2)-fucosylation inhibitor sensitized HCC tumors to sorafenib, a first-line molecularly targeted drug used for advanced HCC patients, and reduced the tumor-initiating subset. FUT1 overexpression and/or CD147, ICAM-1, EGFR, and EPHA2 fucosylation may be good prognostic markers and therapeutic targets for cancer patients.
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