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Fatty acid metabolism in aggressive B-cell lymphoma is inhibited by tetraspanin CD37

Author

Listed:
  • Rens Peeters

    (Radboud University Medical Centre)

  • Jorge Cuenca-Escalona

    (Radboud University Medical Centre)

  • Esther A. Zaal

    (Utrecht University)

  • Anna T. Hoekstra

    (Utrecht University)

  • Anouk C. G. Balvert

    (Radboud University Medical Centre)

  • Marcos Vidal-Manrique

    (Radboud University Medical Centre)

  • Niek Blomberg

    (Leiden University Medical Centre)

  • Sjoerd J. Deventer

    (Radboud University Medical Centre)

  • Rinke Stienstra

    (Wageningen University)

  • Julia Jellusova

    (Technical University Munich
    Technical University Munich)

  • Martin Giera

    (Leiden University Medical Centre)

  • Luciana Hannibal

    (Medical Centre - University of Freiburg)

  • Ute Spiekerkoetter

    (Medical Centre - University of Freiburg)

  • Martin Beest

    (Radboud University Medical Centre)

  • Celia R. Berkers

    (Utrecht University
    Utrecht University)

  • Annemiek B. Spriel

    (Radboud University Medical Centre)

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.

Suggested Citation

  • Rens Peeters & Jorge Cuenca-Escalona & Esther A. Zaal & Anna T. Hoekstra & Anouk C. G. Balvert & Marcos Vidal-Manrique & Niek Blomberg & Sjoerd J. Deventer & Rinke Stienstra & Julia Jellusova & Martin, 2022. "Fatty acid metabolism in aggressive B-cell lymphoma is inhibited by tetraspanin CD37," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33138-7
    DOI: 10.1038/s41467-022-33138-7
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    References listed on IDEAS

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