IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-33138-7.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-33138-7
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-33138-7?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Abigail S. Krall & Shili Xu & Thomas G. Graeber & Daniel Braas & Heather R. Christofk, 2016. "Asparagine promotes cancer cell proliferation through use as an amino acid exchange factor," Nature Communications, Nature, vol. 7(1), pages 1-13, September.
    2. Gloria Pascual & Alexandra Avgustinova & Stefania Mejetta & Mercè Martín & Andrés Castellanos & Camille Stephan-Otto Attolini & Antoni Berenguer & Neus Prats & Agustí Toll & Juan Antonio Hueto & Coro , 2017. "Targeting metastasis-initiating cells through the fatty acid receptor CD36," Nature, Nature, vol. 541(7635), pages 41-45, January.
    3. Sung Hoon Cho & Ariel L. Raybuck & Kristy Stengel & Mei Wei & Thomas C. Beck & Emmanuel Volanakis & James W. Thomas & Scott Hiebert & Volker H. Haase & Mark R. Boothby, 2016. "Germinal centre hypoxia and regulation of antibody qualities by a hypoxia response system," Nature, Nature, vol. 537(7619), pages 234-238, September.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Ping Yang & Hong Qin & Yiyu Li & Anhua Xiao & Enze Zheng & Han Zeng & Chunxiao Su & Xiaoqing Luo & Qiannan Lu & Meng Liao & Lei Zhao & Li Wei & Zac Varghese & John F. Moorhead & Yaxi Chen & Xiong Z. R, 2022. "CD36-mediated metabolic crosstalk between tumor cells and macrophages affects liver metastasis," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    2. C. Megan Young & Laurent Beziaud & Pierre Dessen & Angela Madurga Alonso & Albert Santamaria-Martínez & Joerg Huelsken, 2023. "Metabolic dependencies of metastasis-initiating cells in female breast cancer," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    3. Marta Iborra-Pernichi & Jonathan Ruiz García & María Velasco de la Esperanza & Belén S. Estrada & Elena R. Bovolenta & Claudia Cifuentes & Cristina Prieto Carro & Tamara González Martínez & José Garcí, 2024. "Defective mitochondria remodelling in B cells leads to an aged immune response," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    4. Hongxing Shen & Oluwagbemiga A. Ojo & Haitao Ding & Logan J. Mullen & Chuan Xing & M. Iqbal Hossain & Abdelrahman Yassin & Vivian Y. Shi & Zach Lewis & Ewa Podgorska & Shaida A. Andrabi & Maciek R. An, 2024. "HIF1α-regulated glycolysis promotes activation-induced cell death and IFN-γ induction in hypoxic T cells," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    5. Jan Philipp Menzel & Reuben S. E. Young & Aurélie H. Benfield & Julia S. Scott & Puttandon Wongsomboon & Lukáš Cudlman & Josef Cvačka & Lisa M. Butler & Sónia T. Henriques & Berwyck L. J. Poad & Steph, 2023. "Ozone-enabled fatty acid discovery reveals unexpected diversity in the human lipidome," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    6. Daniela Michelatti & Sven Beyes & Chiara Bernardis & Maria Luce Negri & Leonardo Morelli & Naiara Garcia Bediaga & Vittoria Poli & Luca Fagnocchi & Sara Lago & Sarah D’Annunzio & Nicole Cona & Ilaria , 2024. "Oncogenic enhancers prime quiescent metastatic cells to escape NK immune surveillance by eliciting transcriptional memory," Nature Communications, Nature, vol. 15(1), pages 1-24, December.
    7. Phillip M. Brailey & Lauren Evans & Juan Carlos López-Rodríguez & Anthony Sinadinos & Victoria Tyrrel & Gavin Kelly & Valerie O’Donnell & Peter Ghazal & Susan John & Patricia Barral, 2022. "CD1d-dependent rewiring of lipid metabolism in macrophages regulates innate immune responses," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    8. Bonnie Huang & James D. Phelan & Silvia Preite & Julio Gomez-Rodriguez & Kristoffer H. Johansen & Hirofumi Shibata & Arthur L. Shaffer & Qin Xu & Brendan Jeffrey & Martha Kirby & Stacie Anderson & Yan, 2022. "In vivo CRISPR screens reveal a HIF-1α-mTOR-network regulates T follicular helper versus Th1 cells," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    9. Qiming Zhou & Yao Peng & Fenfen Ji & Huarong Chen & Wei Kang & Lam-Shing Chan & Hongyan Gou & Yufeng Lin & Pingmei Huang & Danyu Chen & Qinyao Wei & Hao Su & Cong Liang & Xiang Zhang & Jun Yu & Chi Ch, 2023. "Targeting of SLC25A22 boosts the immunotherapeutic response in KRAS-mutant colorectal cancer," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    10. Wenna Chi & Na Kang & Linlin Sheng & Sichen Liu & Lei Tao & Xizhi Cao & Ye Liu & Can Zhu & Yuming Zhang & Bolong Wu & Ruiqun Chen & Lili Cheng & Jing Wang & Xiaolin Sun & Xiaohui Liu & Haiteng Deng & , 2024. "MCT1-governed pyruvate metabolism is essential for antibody class-switch recombination through H3K27 acetylation," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    11. Sophie Hillion & Anjelica Miranda & Christelle Dantec & Marina Boudigou & Laëtitia Pottier & Divi Cornec & Raul M. Torres & Roberta Pelanda, 2024. "Maf expression in B cells restricts reactive plasmablast and germinal center B cell expansion," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    12. Rebekka Wegmann & Ximena Bonilla & Ruben Casanova & Stéphane Chevrier & Ricardo Coelho & Cinzia Esposito & Joanna Ficek-Pascual & Sandra Goetze & Gabriele Gut & Francis Jacob & Andrea Jacobs & Jack Ku, 2024. "Single-cell landscape of innate and acquired drug resistance in acute myeloid leukemia," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    13. Yuying Tan & Junjie Li & Guangyuan Zhao & Kai-Chih Huang & Horacio Cardenas & Yinu Wang & Daniela Matei & Ji-Xin Cheng, 2022. "Metabolic reprogramming from glycolysis to fatty acid uptake and beta-oxidation in platinum-resistant cancer cells," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    14. Ling Tao & Mahmoud A. Mohammad & Giorgio Milazzo & Myrthala Moreno-Smith & Tajhal D. Patel & Barry Zorman & Andrew Badachhape & Blanca E. Hernandez & Amber B. Wolf & Zihua Zeng & Jennifer H. Foster & , 2022. "MYCN-driven fatty acid uptake is a metabolic vulnerability in neuroblastoma," Nature Communications, Nature, vol. 13(1), pages 1-17, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33138-7. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.