ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2016
Role of neutral ceramidase in colon cancer.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 74 citations in OpenAlex.
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- QTL Mapping-Based Identification of Visceral White-Nodules Disease Resistance Genes inInternational journal of molecular sciences · 2024Article
- The diverse roles of sphingolipids in inflammatory bowel disease.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Review
- Sphingolipids: Less Enigmatic but Still Many Questions about the Role(s) of Ceramide in the Synthesis/Function of the Ganglioside Class of Glycosphingolipids.International journal of molecular sciences · 2024Review
- Therapeutic Potential for Sphingolipids in Inflammatory Bowel Disease and Colorectal Cancer.Cancers · 2024Review
- Effects of N6-methyladenosine modification on metabolic reprogramming in digestive tract tumors.Heliyon · 2024Review
- The role of ACER2 in intestinal sphingolipid metabolism and gastrointestinal cancers.Frontiers in immunology · 2024Review
- High-throughput discovery of novel small-molecule inhibitors of acid Ceramidase.Journal of enzyme inhibition and medicinal chemistry · 2023Article
- Neutral ceramidase-active site inhibitor chemotypes and binding modes.Bioorganic chemistry · 2023Article
- The Effect of Silencing the Genes Responsible for the Level of Sphingosine-1-phosphate on the Apoptosis of Colon Cancer Cells.International journal of molecular sciences · 2023Article
- LARP6 suppresses colorectal cancer progression through ZNF267/SGMS2-mediated imbalance of sphingomyelin synthesis.Journal of experimental & clinical cancer research : CR · 2023Article
- Mysterious sphingolipids: metabolic interrelationships at the center of pathophysiology.Frontiers in physiology · 2023Review
- Lipid-lowering drugs affect lung cancer risk via sphingolipid metabolism: a drug-target Mendelian randomization study.Frontiers in genetics · 2023Article
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14 authors at 6 institutions in 2 countries.
Funding
Abstract
Alterations in sphingolipid metabolism, especially ceramide and sphingosine 1-phosphate, have been linked to colon cancer, suggesting that enzymes of sphingolipid metabolism may emerge as novel regulators and targets in colon cancer. Neutral ceramidase (nCDase), a key enzyme in sphingolipid metabolism that hydrolyzes ceramide into sphingosine, is highly expressed in the intestine; however, its role in colon cancer has not been defined. Here we show that molecular and pharmacological inhibition of nCDase in colon cancer cells increases ceramide, and this is accompanied by decreased cell survival and increased apoptosis and autophagy, with minimal effects on noncancerous cells. Inhibition of nCDase resulted in loss of β-catenin and inhibition of ERK, components of pathways relevant for colon cancer development. Furthermore, inhibition of nCDase in a xenograft model delayed tumor growth and increased ceramide while decreasing proliferation. It is noteworthy that mice lacking nCDase treated with azoxymethane were protected from tumor formation. Taken together, these studies show that nCDase is pivotal for regulating initiation and development of colon cancer, and these data suggest that this enzyme is a suitable and novel target for colon cancer therapy.-García-Barros, M., Coant, N., Kawamori, T., Wada, M., Snider, A. J., Truman, J.-P., Wu, B. X., Furuya, H., Clarke, C. J., Bialkowska, A. B., Ghaleb, A., Yang, V. W., Obeid, L. M., Hannun, Y. A. Role of neutral ceramidase in colon cancer.
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