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Evidence for an alternative fatty acid desaturation pathway increasing cancer plasticity

Author

Listed:
  • Kim Vriens

    (VIB-KU Leuven Center for Cancer Biology, VIB
    KU Leuven and Leuven Cancer Institute (LKI))

  • Stefan Christen

    (VIB-KU Leuven Center for Cancer Biology, VIB
    KU Leuven and Leuven Cancer Institute (LKI))

  • Sweta Parik

    (VIB-KU Leuven Center for Cancer Biology, VIB
    KU Leuven and Leuven Cancer Institute (LKI)
    Vrije Universiteit Brussel
    VIB Center for Inflammation Research)

  • Dorien Broekaert

    (VIB-KU Leuven Center for Cancer Biology, VIB
    KU Leuven and Leuven Cancer Institute (LKI))

  • Kazuaki Yoshinaga

    (Tsukishima Foods Industry
    Fukushima University)

  • Ali Talebi

    (Leuven Cancer Institute (LKI))

  • Jonas Dehairs

    (Leuven Cancer Institute (LKI))

  • Carmen Escalona-Noguero

    (VIB-KU Leuven Center for Cancer Biology, VIB
    KU Leuven and Leuven Cancer Institute (LKI))

  • Roberta Schmieder

    (VIB-KU Leuven Center for Cancer Biology, VIB
    KU Leuven and Leuven Cancer Institute (LKI))

  • Thomas Cornfield

    (University of Oxford, Churchill Hospital)

  • Catriona Charlton

    (University of Oxford, Churchill Hospital)

  • Laura Romero-Pérez

    (Institute of Pathology, Faculty of Medicine, LMU Munich)

  • Matteo Rossi

    (VIB-KU Leuven Center for Cancer Biology, VIB
    KU Leuven and Leuven Cancer Institute (LKI))

  • Gianmarco Rinaldi

    (VIB-KU Leuven Center for Cancer Biology, VIB
    KU Leuven and Leuven Cancer Institute (LKI))

  • Martin F. Orth

    (Institute of Pathology, Faculty of Medicine, LMU Munich)

  • Ruben Boon

    (KU Leuven)

  • Axelle Kerstens

    (KU Leuven
    KU Leuven)

  • Suet Ying Kwan

    (University of Texas MD Anderson Cancer Center)

  • Brandon Faubert

    (UT Southwestern)

  • Andrés Méndez-Lucas

    (The Francis Crick Institute)

  • Charlotte C. Kopitz

    (Pharmaceuticals)

  • Ting Chen

    (Smilow Research Center)

  • Juan Fernandez-Garcia

    (VIB-KU Leuven Center for Cancer Biology, VIB
    KU Leuven and Leuven Cancer Institute (LKI))

  • João A. G. Duarte

    (VIB-KU Leuven Center for Cancer Biology, VIB
    KU Leuven and Leuven Cancer Institute (LKI))

  • Arndt A. Schmitz

    (Pharmaceuticals)

  • Patrick Steigemann

    (Pharmaceuticals)

  • Mustapha Najimi

    (Université Catholique de Louvain and Cliniques Universitaires St Luc)

  • Andrea Hägebarth

    (Pharmaceuticals)

  • Jo A. Ginderachter

    (Vrije Universiteit Brussel
    VIB Center for Inflammation Research)

  • Etienne Sokal

    (Université Catholique de Louvain and Cliniques Universitaires St Luc)

  • Naohiro Gotoh

    (Tokyo University of Marine Science and Technology)

  • Kwok-Kin Wong

    (Smilow Research Center)

  • Catherine Verfaillie

    (KU Leuven)

  • Rita Derua

    (KU Leuven)

  • Sebastian Munck

    (KU Leuven
    KU Leuven)

  • Mariia Yuneva

    (The Francis Crick Institute)

  • Laura Beretta

    (University of Texas MD Anderson Cancer Center)

  • Ralph J. DeBerardinis

    (UT Southwestern
    UT Southwestern Medical Center)

  • Johannes V. Swinnen

    (Leuven Cancer Institute (LKI))

  • Leanne Hodson

    (University of Oxford, Churchill Hospital)

  • David Cassiman

    (KU Leuven
    Metabolism and Ageing, KU Leuven)

  • Chris Verslype

    (KU Leuven
    KU Leuven)

  • Sven Christian

    (Pharmaceuticals)

  • Sylvia Grünewald

    (Pharmaceuticals)

  • Thomas G. P. Grünewald

    (Institute of Pathology, Faculty of Medicine, LMU Munich
    Institute of Pathology, Faculty of Medicine, LMU Munich
    German Cancer Consortium (DKTK), Partner site Munich
    German Cancer Research Center (DKFZ))

  • Sarah-Maria Fendt

    (VIB-KU Leuven Center for Cancer Biology, VIB
    KU Leuven and Leuven Cancer Institute (LKI))

Abstract

Most tumours have an aberrantly activated lipid metabolism1,2 that enables them to synthesize, elongate and desaturate fatty acids to support proliferation. However, only particular subsets of cancer cells are sensitive to approaches that target fatty acid metabolism and, in particular, fatty acid desaturation3. This suggests that many cancer cells contain an unexplored plasticity in their fatty acid metabolism. Here we show that some cancer cells can exploit an alternative fatty acid desaturation pathway. We identify various cancer cell lines, mouse hepatocellular carcinomas, and primary human liver and lung carcinomas that desaturate palmitate to the unusual fatty acid sapienate to support membrane biosynthesis during proliferation. Accordingly, we found that sapienate biosynthesis enables cancer cells to bypass the known fatty acid desaturation pathway that is dependent on stearoyl-CoA desaturase. Thus, only by targeting both desaturation pathways is the in vitro and in vivo proliferation of cancer cells that synthesize sapienate impaired. Our discovery explains metabolic plasticity in fatty acid desaturation and constitutes an unexplored metabolic rewiring in cancers.

Suggested Citation

  • Kim Vriens & Stefan Christen & Sweta Parik & Dorien Broekaert & Kazuaki Yoshinaga & Ali Talebi & Jonas Dehairs & Carmen Escalona-Noguero & Roberta Schmieder & Thomas Cornfield & Catriona Charlton & La, 2019. "Evidence for an alternative fatty acid desaturation pathway increasing cancer plasticity," Nature, Nature, vol. 566(7744), pages 403-406, February.
  • Handle: RePEc:nat:nature:v:566:y:2019:i:7744:d:10.1038_s41586-019-0904-1
    DOI: 10.1038/s41586-019-0904-1
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    Citations

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    Cited by:

    1. 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.
    2. Zidan Wang & Donghui Zhang & Junhan Wu & Wenpeng Zhang & Yu Xia, 2024. "Illuminating the dark space of neutral glycosphingolipidome by selective enrichment and profiling at multi-structural levels," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    3. Shashank Dadsena & Rodrigo Cuevas Arenas & Gonçalo Vieira & Susanne Brodesser & Manuel N. Melo & Ana J. García-Sáez, 2024. "Lipid unsaturation promotes BAX and BAK pore activity during apoptosis," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    4. Tian Xia & Feng Zhou & Donghui Zhang & Xue Jin & Hengxue Shi & Hang Yin & Yanqing Gong & Yu Xia, 2023. "Deep-profiling of phospholipidome via rapid orthogonal separations and isomer-resolved mass spectrometry," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    5. Bennett W. Fox & Maximilian J. Helf & Russell N. Burkhardt & Alexander B. Artyukhin & Brian J. Curtis & Diana Fajardo Palomino & Allen F. Schroeder & Amaresh Chaturbedi & Arnaud Tauffenberger & Cheste, 2024. "Evolutionarily related host and microbial pathways regulate fat desaturation in C. elegans," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    6. Yanying Wang & Jing Wang & Xiaoyu Li & Xushen Xiong & Jianyi Wang & Ziheng Zhou & Xiaoxiao Zhu & Yang Gu & Dan Dominissini & Lei He & Yong Tian & Chengqi Yi & Zusen Fan, 2021. "N1-methyladenosine methylation in tRNA drives liver tumourigenesis by regulating cholesterol metabolism," Nature Communications, Nature, vol. 12(1), pages 1-19, December.

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