ArticleCell death and differentiation2025
UGT8 mediated sulfatide synthesis modulates BAX localization and dictates apoptosis sensitivity of colorectal cancer.
Article in Cell death and differentiation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- Natural polysaccharides targeting mitochondrial function for colorectal cancer prevention and treatment: mechanisms and nano-delivery strategies.Chinese medicine · 2026Review
- Host transcriptomic analysis reveals a defective intracellular environment that limits SARS-CoV-2 replication in CFTR-deficient airway epithelium.Frontiers in cellular and infection microbiology · 2026Article
- pH-responsive magnetic FeMaterials today. Bio · 2025Article
- Article
- GSK-3 and BCL-XL inhibition mitigates the competitive advantage of APC-mutant colorectal cancer cells.Oncogenesis · 2025Article
- Cholesterol-activated stress granules reduce the membrane localization of DRD2 and promote prolactinoma dopamine agonists resistance.Acta neuropathologica communications · 2025Article
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Authors and funding
10 authors.
Funding
Abstract
Elevated de novo lipid synthesis is a remarkable adaptation of cancer cells that can be exploited for therapy. However, the role of altered lipid metabolism in the regulation of apoptosis is still poorly understood. Using thermal proteome profiling, we identified Manidipine-2HCl, targeting UGT8, a key enzyme in the synthesis of sulfatides. In agreement, lipidomic analysis indicated that sulfatides are strongly reduced in colorectal cancer cells upon treatment with Manidipine-2HCl. Intriguingly, this reduction led to severe mitochondrial swelling and a strong synergism with BH3 mimetics targeting BCL-XL, leading to the activation of mitochondria-dependent apoptosis. Mechanistically, Manidipine-2HCl enhanced mitochondrial BAX localization in a sulfatide-dependent fashion, facilitating its activation by BH3 mimetics. In conclusion, our data indicates that UGT8 mediated synthesis of sulfatides controls mitochondrial homeostasis and BAX localization, dictating apoptosis sensitivity of colorectal cancer cells.
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