1. Fatty acid metabolism in aggressive B-cell lymphoma is inhibited by tetraspanin CD37
- Author
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Peeters, Rens, Cuenca-Escalona, Jorge, Zaal, Esther A., Hoekstra, Anna T., Balvert, Anouk C.G., Vidal-Manrique, Marcos, Blomberg, Niek, van Deventer, Sjoerd J., Stienstra, Rinke, Jellusova, Julia, Giera, Martin, Hannibal, Luciana, Spiekerkoetter, Ute, ter Beest, Martin, Berkers, Celia R., van Spriel, Annemiek B., Veterinaire biochemie, Sub Biomol.Mass Spectrometry & Proteom., Faculteit Diergeneeskunde, Biomolecular Mass Spectrometry and Proteomics, Veterinaire biochemie, Sub Biomol.Mass Spectrometry & Proteom., Faculteit Diergeneeskunde, and Biomolecular Mass Spectrometry and Proteomics
- Subjects
Lymphoma, B-Cell ,Chemistry(all) ,Tetraspanins ,Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2] ,Palmitates ,lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4] ,General Physics and Astronomy ,Physics and Astronomy(all) ,Biochemistry ,General Biochemistry, Genetics and Molecular Biology ,Mice ,Voeding, Metabolisme en Genomica ,All institutes and research themes of the Radboud University Medical Center ,Voeding ,Antigens, Neoplasm ,Animals ,Life Science ,General ,Nutrition ,Multidisciplinary ,Biochemistry, Genetics and Molecular Biology(all) ,Fatty Acids ,Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6] ,General Chemistry ,Metabolism and Genomics ,Metabolisme en Genomica ,Nutrition, Metabolism and Genomics ,Genetics and Molecular Biology(all) - Abstract
The importance of fatty acid (FA) metabolism in cancer is well-established, yet the mechanisms underlying metabolic reprogramming remain elusive. Here, we identify tetraspanin CD37, a prognostic marker for aggressive B-cell lymphoma, as essential membrane-localized inhibitor of FA metabolism. Deletion of CD37 on lymphoma cells results in increased FA oxidation shown by functional assays and metabolomics. Furthermore, CD37-negative lymphomas selectively deplete palmitate from serum in mouse studies. Mechanistically, CD37 inhibits the FA transporter FATP1 through molecular interaction. Consequently, deletion of CD37 induces uptake and processing of exogenous palmitate into energy and essential building blocks for proliferation, and inhibition of FATP1 reverses this phenotype. Large lipid deposits and intracellular lipid droplets are observed in CD37-negative lymphoma tissues of patients. Moreover, inhibition of carnitine palmitoyl transferase 1 A significantly compromises viability and proliferation of CD37-deficient lymphomas. Collectively, our results identify CD37 as a direct gatekeeper of the FA metabolic switch in aggressive B-cell lymphoma.Tetraspanin CD37 deficiency has been reported as a prognostic marker for aggressive B-cell lymphoma. Here, the authors show that CD37 interacts with the fatty acid transporter 1 to inhibit palmitate uptake and its deficiency leads to increased fatty acid metabolism which promotes tumorigenesis in B-cell lymphoma.
- Published
- 2022