IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-32101-w.html
   My bibliography  Save this article

Metabolic reprogramming from glycolysis to fatty acid uptake and beta-oxidation in platinum-resistant cancer cells

Author

Listed:
  • Yuying Tan

    (Boston University)

  • Junjie Li

    (Boston University)

  • Guangyuan Zhao

    (Northwestern University)

  • Kai-Chih Huang

    (Boston University)

  • Horacio Cardenas

    (Northwestern University)

  • Yinu Wang

    (Northwestern University)

  • Daniela Matei

    (Northwestern University
    Robert H. Lurie Comprehensive Cancer Center)

  • Ji-Xin Cheng

    (Boston University
    Boston University
    Boston University)

Abstract

Increased glycolysis is considered as a hallmark of cancer. Yet, cancer cell metabolic reprograming during therapeutic resistance development is under-studied. Here, through high-throughput stimulated Raman scattering imaging and single cell analysis, we find that cisplatin-resistant cells exhibit increased fatty acids (FA) uptake, accompanied by decreased glucose uptake and lipogenesis, indicating reprogramming from glucose to FA dependent anabolic and energy metabolism. A metabolic index incorporating glucose derived anabolism and FA uptake correlates linearly to the level of cisplatin resistance in ovarian cancer (OC) cell lines and primary cells. The increased FA uptake facilitates cancer cell survival under cisplatin-induced oxidative stress by enhancing beta-oxidation. Consequently, blocking beta-oxidation by a small molecule inhibitor combined with cisplatin or carboplatin synergistically suppresses OC proliferation in vitro and growth of patient-derived xenografts in vivo. Collectively, these findings support a rapid detection method of cisplatin-resistance at single cell level and a strategy for treating cisplatin-resistant tumors.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32101-w
    DOI: 10.1038/s41467-022-32101-w
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-32101-w
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-32101-w?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. Alexia Karen Cotte & Virginie Aires & Maxime Fredon & Emeric Limagne & Valentin Derangère & Marion Thibaudin & Etienne Humblin & Alessandra Scagliarini & Jean-Paul Pais Barros & Patrick Hillon & Franç, 2018. "Lysophosphatidylcholine acyltransferase 2-mediated lipid droplet production supports colorectal cancer chemoresistance," Nature Communications, Nature, vol. 9(1), pages 1-16, December.
    2. Jiajun Du & Yapeng Su & Chenxi Qian & Dan Yuan & Kun Miao & Dongkwan Lee & Alphonsus H. C. Ng & Reto S. Wijker & Antoni Ribas & Raphael D. Levine & James R. Heath & Lu Wei, 2020. "Raman-guided subcellular pharmaco-metabolomics for metastatic melanoma cells," Nature Communications, Nature, vol. 11(1), pages 1-16, December.
    3. Cristovão M. Sousa & Douglas E. Biancur & Xiaoxu Wang & Christopher J. Halbrook & Mara H. Sherman & Li Zhang & Daniel Kremer & Rosa F. Hwang & Agnes K. Witkiewicz & Haoqiang Ying & John M. Asara & Ron, 2016. "Erratum: Pancreatic stellate cells support tumour metabolism through autophagic alanine secretion," Nature, Nature, vol. 540(7631), pages 150-150, December.
    4. 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.
    5. Cristovão M. Sousa & Douglas E. Biancur & Xiaoxu Wang & Christopher J. Halbrook & Mara H. Sherman & Li Zhang & Daniel Kremer & Rosa F. Hwang & Agnes K. Witkiewicz & Haoqiang Ying & John M. Asara & Ron, 2016. "Pancreatic stellate cells support tumour metabolism through autophagic alanine secretion," Nature, Nature, vol. 536(7617), pages 479-483, August.
    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. Ali Vaziri-Gohar & Jonathan J. Hue & Ata Abbas & Hallie J. Graor & Omid Hajihassani & Mehrdad Zarei & George Titomihelakis & John Feczko & Moeez Rathore & Sylwia Chelstowska & Alexander W. Loftus & Ru, 2023. "Increased glucose availability sensitizes pancreatic cancer to chemotherapy," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    2. Xianbing Zhu & Zheng Fu & Shary Y. Chen & Dionzie Ong & Giulio Aceto & Rebecca Ho & Jutta Steinberger & Anie Monast & Virginie Pilon & Eunice Li & Monica Ta & Kyle Ching & Bianca N. Adams & Gian L. Ne, 2023. "Alanine supplementation exploits glutamine dependency induced by SMARCA4/2-loss," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    3. 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.
    4. 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.
    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. Tin-Lok Wong & Jia-Jian Loh & Shixun Lu & Helen H. N. Yan & Hoi Cheong Siu & Ren Xi & Dessy Chan & Max J. F. Kam & Lei Zhou & Man Tong & John A. Copland & Leilei Chen & Jing-Ping Yun & Suet Yi Leung &, 2023. "ADAR1-mediated RNA editing of SCD1 drives drug resistance and self-renewal in gastric cancer," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    8. 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.
    9. 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.
    10. 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.
    11. Manuel Sigle & Anne-Katrin Rohlfing & Martin Kenny & Sophia Scheuermann & Na Sun & Ulla Graeßner & Verena Haug & Jessica Sudmann & Christian M. Seitz & David Heinzmann & Katja Schenke-Layland & Patric, 2023. "Translating genomic tools to Raman spectroscopy analysis enables high-dimensional tissue characterization on molecular resolution," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    12. Hyemin Lee & Amber Horbath & Lavanya Kondiparthi & Jitendra Kumar Meena & Guang Lei & Shayani Dasgupta & Xiaoguang Liu & Li Zhuang & Pranavi Koppula & Mi Li & Iqbal Mahmud & Bo Wei & Philip L. Lorenzi, 2024. "Cell cycle arrest induces lipid droplet formation and confers ferroptosis resistance," Nature Communications, Nature, vol. 15(1), pages 1-13, 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_s41467-022-32101-w. 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.