ArticleCell death & disease2023
FDW028, a novel FUT8 inhibitor, impels lysosomal proteolysis of B7-H3 via chaperone-mediated autophagy pathway and exhibits potent efficacy against metastatic colorectal cancer.
Article in Cell death & disease, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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40 citing papers in PubMed, 47 citations in OpenAlex.
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- Fucosyltransferases in asthma: regulators of epithelial dysfunction, senescence, and airway inflammation.Clinical reviews in allergy & immunology · 2026Review
- The glycobiology of prostate cancer: an update.Oncogene · 2026Review
- Protein modification systems as cancer biomarkers and therapeutic targets.Precision clinical medicine · 2026Review
- FUT8-mediated core fucosylation of receptor APN drives entry of multiple alphacoronaviruses.PLoS pathogens · 2026Article
- N-glycan signatures of immunoglobulins-depleted serum proteins in colorectal cancer.Glycoconjugate journal · 2026Article
- Therapeutic targeting of cancer stem cell-specific surface glycans and glycoproteins.Discover oncology · 2026Review
- Exploiting human fucosyltransferase 8 allostery with a covalent inhibitor for core fucosylation suppression.Nature communications · 2026Article
- Autophagy regulation of pyroptosis and ferroptosis: a new strategy for colorectal cancer treatment.Apoptosis : an international journal on programmed cell death · 2026Review
- POFUT2 Mediated Fucosylation of JUP Enhances VEGFA Expression to Promote Angiogenesis in Colorectal Cancer.International journal of medical sciences · 2026Article
- Enzymatic glycosylation as a potential molecular link between Alzheimer's disease and glaucoma.International journal of ophthalmology · 2026Review
- Glycosylation of B7-H3 Promotes CD8International journal of biological sciences · 2026Article
- Fucose metabolism as a central axis linking inflammation, immunity, and cancer in the gut.Frontiers in immunology · 2026Review
- Golgi Drivers of Cancer.Sub-cellular biochemistry · 2026Review
- Targeting the autophagic network: A new frontier in colorectal cancer chemotherapy response.CytoJournal · 2026Article
- Immunoregulatory roles of post-translational modifications in colorectal cancer: mechanisms and therapeutic implications.Cellular and molecular life sciences : CMLS · 2025Review
- Structure, function, and implications of fucosyltransferases in health and disease.Nature communications · 2025Review
- Article
- PARP inhibitors accumulate B7-H3 on fibroblasts via blocking autophagic flux to potentiate immune evasion in ovarian cancer.Oncoimmunology · 2025Article
Corrections and comments
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Authors and funding
21 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metastatic colorectal cancer (mCRC) is a major cause of cancer-related mortality due to the absence of effective therapeutics. Thus, it is urgent to discover new drugs for mCRC. Fucosyltransferase 8 (FUT8) is a potential therapeutic target with high level in most malignant cancers including CRC. FUT8 mediates the core fucosylation of CD276 (B7-H3), a key immune checkpoint molecule (ICM), in CRC. FUT8-silence-induced defucosylation at N104 on B7-H3 attracts heat shock protein family A member 8 (HSPA8, also known as HSC70) to bind with 106-110 SLRLQ motif and consequently propels lysosomal proteolysis of B7-H3 through the chaperone-mediated autophagy (CMA) pathway. Then we report the development and characterization of a potent and highly selective small-molecule inhibitor of FUT8, named FDW028, which evidently prolongs the survival of mice with CRC pulmonary metastases (CRPM). FDW028 exhibits potent anti-tumor activity by defucosylation and impelling lysosomal degradation of B7-H3 through the CMA pathway. Taken together, FUT8 inhibition destabilizes B7-H3 through CMA-mediated lysosomal proteolysis, and FDW028 acts as a potent therapeutic candidate against mCRC by targeting FUT8. FDW028, an inhibitor specifically targeted FUT8, promotes defucosylation and consequent HSC70/LAMP2A-mediated lysosomal degradation of B7-H3, and exhibits potent anti-mCRC activities.
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