IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-42748-8.html
   My bibliography  Save this article

Metabolic dependencies of metastasis-initiating cells in female breast cancer

Author

Listed:
  • C. Megan Young

    (École Polytechnique Fédérale de Lausanne (EPFL), ISREC (Swiss Institute for Experimental Cancer Research)
    Agora Cancer Research Center
    Swiss Cancer Center Léman)

  • Laurent Beziaud

    (École Polytechnique Fédérale de Lausanne (EPFL), ISREC (Swiss Institute for Experimental Cancer Research)
    Agora Cancer Research Center
    Swiss Cancer Center Léman)

  • Pierre Dessen

    (École Polytechnique Fédérale de Lausanne (EPFL), ISREC (Swiss Institute for Experimental Cancer Research)
    Agora Cancer Research Center
    Swiss Cancer Center Léman)

  • Angela Madurga Alonso

    (École Polytechnique Fédérale de Lausanne (EPFL), ISREC (Swiss Institute for Experimental Cancer Research)
    Agora Cancer Research Center
    Swiss Cancer Center Léman)

  • Albert Santamaria-Martínez

    (École Polytechnique Fédérale de Lausanne (EPFL), ISREC (Swiss Institute for Experimental Cancer Research)
    Swiss Cancer Center Léman)

  • Joerg Huelsken

    (École Polytechnique Fédérale de Lausanne (EPFL), ISREC (Swiss Institute for Experimental Cancer Research)
    Agora Cancer Research Center
    Swiss Cancer Center Léman)

Abstract

Understanding the mechanisms that enable cancer cells to metastasize is essential in preventing cancer progression. Here we examine the metabolic adaptations of metastasis-initiating cells (MICs) in female breast cancer and how those shape their metastatic phenotype. We find that endogenous MICs depend on the oxidative tricarboxylic acid cycle and fatty acid usage. Sorting tumor cells based upon solely mitochondrial membrane potential or lipid storage is sufficient at identifying MICs. We further identify that mitochondrially-generated citrate is exported to the cytoplasm to yield acetyl-CoA, and this is crucial to maintaining heightened levels of H3K27ac in MICs. Blocking acetyl-CoA generating pathways or H3K27ac-specific epigenetic writers and readers reduces expression of epithelial-to-mesenchymal related genes, MIC frequency, and metastatic potential. Exogenous supplementation of a short chain carboxylic acid, acetate, increases MIC frequency and metastasis. In patient cohorts, we observe that higher expression of oxidative phosphorylation related genes is associated with reduced distant relapse-free survival. These data demonstrate that MICs specifically and precisely alter their metabolism to efficiently colonize distant organs.

Suggested Citation

  • 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.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42748-8
    DOI: 10.1038/s41467-023-42748-8
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-42748-8
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-023-42748-8?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. Jaekyoung Son & Costas A. Lyssiotis & Haoqiang Ying & Xiaoxu Wang & Sujun Hua & Matteo Ligorio & Rushika M. Perera & Cristina R. Ferrone & Edouard Mullarky & Ng Shyh-Chang & Ya’an Kang & Jason B. Flem, 2013. "Correction: Corrigendum: Glutamine supports pancreatic cancer growth through a KRAS-regulated metabolic pathway," Nature, Nature, vol. 499(7459), pages 504-504, July.
    2. Ilaria Malanchi & Albert Santamaria-Martínez & Evelyn Susanto & Hong Peng & Hans-Anton Lehr & Jean-Francois Delaloye & Joerg Huelsken, 2012. "Interactions between cancer stem cells and their niche govern metastatic colonization," Nature, Nature, vol. 481(7379), pages 85-89, January.
    3. Mahmoud Ghandi & Franklin W. Huang & Judit Jané-Valbuena & Gregory V. Kryukov & Christopher C. Lo & E. Robert McDonald & Jordi Barretina & Ellen T. Gelfand & Craig M. Bielski & Haoxin Li & Kevin Hu & , 2019. "Next-generation characterization of the Cancer Cell Line Encyclopedia," Nature, Nature, vol. 569(7757), pages 503-508, May.
    4. Jaekyoung Son & Costas A. Lyssiotis & Haoqiang Ying & Xiaoxu Wang & Sujun Hua & Matteo Ligorio & Rushika M. Perera & Cristina R. Ferrone & Edouard Mullarky & Ng Shyh-Chang & Ya’an Kang & Jason B. Flem, 2013. "Glutamine supports pancreatic cancer growth through a KRAS-regulated metabolic pathway," Nature, Nature, vol. 496(7443), pages 101-105, April.
    5. Ilaria Elia & Matteo Rossi & Steve Stegen & Dorien Broekaert & Ginevra Doglioni & Marit van Gorsel & Ruben Boon & Carmen Escalona-Noguero & Sophie Torrekens & Catherine Verfaillie & Erik Verbeken & Ge, 2019. "Breast cancer cells rely on environmental pyruvate to shape the metastatic niche," Nature, Nature, vol. 568(7750), pages 117-121, April.
    6. Lei Jiang & Alexander A. Shestov & Pamela Swain & Chendong Yang & Seth J. Parker & Qiong A. Wang & Lance S. Terada & Nicholas D. Adams & Michael T. McCabe & Beth Pietrak & Stan Schmidt & Christian M. , 2016. "Reductive carboxylation supports redox homeostasis during anchorage-independent growth," Nature, Nature, vol. 532(7598), pages 255-258, April.
    7. 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.
    8. Xin Jin & Zelalem Demere & Karthik Nair & Ahmed Ali & Gino B. Ferraro & Ted Natoli & Amy Deik & Lia Petronio & Andrew A. Tang & Cong Zhu & Li Wang & Danny Rosenberg & Vamsi Mangena & Jennifer Roth & K, 2020. "A metastasis map of human cancer cell lines," Nature, Nature, vol. 588(7837), pages 331-336, December.
    9. Ievgenia Pastushenko & Audrey Brisebarre & Alejandro Sifrim & Marco Fioramonti & Tatiana Revenco & Soufiane Boumahdi & Alexandra Van Keymeulen & Daniel Brown & Virginie Moers & Sophie Lemaire & Sarah , 2018. "Identification of the tumour transition states occurring during EMT," Nature, Nature, vol. 556(7702), pages 463-468, April.
    10. Zachary T. Schafer & Alexandra R. Grassian & Loling Song & Zhenyang Jiang & Zachary Gerhart-Hines & Hanna Y. Irie & Sizhen Gao & Pere Puigserver & Joan S. Brugge, 2009. "Antioxidant and oncogene rescue of metabolic defects caused by loss of matrix attachment," Nature, Nature, vol. 461(7260), pages 109-113, September.
    11. Xue Gao & Shu-Hai Lin & Feng Ren & Jin-Tao Li & Jia-Jia Chen & Chuan-Bo Yao & Hong-Bin Yang & Shu-Xia Jiang & Guo-Quan Yan & Di Wang & Yi Wang & Ying Liu & Zongwei Cai & Ying-Ying Xu & Jing Chen & Wen, 2016. "Acetate functions as an epigenetic metabolite to promote lipid synthesis under hypoxia," Nature Communications, Nature, vol. 7(1), pages 1-14, September.
    12. Naama Kanarek & Heather R. Keys & Jason R. Cantor & Caroline A. Lewis & Sze Ham Chan & Tenzin Kunchok & Monther Abu-Remaileh & Elizaveta Freinkman & Lawrence D. Schweitzer & David M. Sabatini, 2018. "Histidine catabolism is a major determinant of methotrexate sensitivity," Nature, Nature, vol. 559(7715), pages 632-636, July.
    13. Rachel J. Perry & Liang Peng & Natasha A. Barry & Gary W. Cline & Dongyan Zhang & Rebecca L. Cardone & Kitt Falk Petersen & Richard G. Kibbey & Andrew L. Goodman & Gerald I. Shulman, 2016. "Acetate mediates a microbiome–brain–β-cell axis to promote metabolic syndrome," Nature, Nature, vol. 534(7606), pages 213-217, June.
    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. Iqbal Mahmud & Guimei Tian & Jia Wang & Tarun E. Hutchinson & Brandon J. Kim & Nikee Awasthee & Seth Hale & Chengcheng Meng & Allison Moore & Liming Zhao & Jessica E. Lewis & Aaron Waddell & Shangtao , 2023. "DAXX drives de novo lipogenesis and contributes to tumorigenesis," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    2. Kimberley McGrail & Paula Granado-Martínez & Rosaura Esteve-Puig & Sara García-Ortega & Yuxin Ding & Sara Sánchez-Redondo & Berta Ferrer & Javier Hernandez-Losa & Francesc Canals & Anna Manzano & Aura, 2022. "BRAF activation by metabolic stress promotes glycolysis sensitizing NRASQ61-mutated melanomas to targeted therapy," Nature Communications, Nature, vol. 13(1), pages 1-22, December.
    3. Guidantonio Malagoli Tagliazucchi & Anna J. Wiecek & Eloise Withnell & Maria Secrier, 2023. "Genomic and microenvironmental heterogeneity shaping epithelial-to-mesenchymal trajectories in cancer," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    4. Taiqi Chen & Siyi Xie & Jie Cheng & Qiao Zhao & Hong Wu & Peng Jiang & Wenjing Du, 2024. "AKT1 phosphorylation of cytoplasmic ME2 induces a metabolic switch to glycolysis for tumorigenesis," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    5. Mahmoud A. Bassal & Saumya E. Samaraweera & Kelly Lim & Brooks A. Benard & Sheree Bailey & Satinder Kaur & Paul Leo & John Toubia & Chloe Thompson-Peach & Tran Nguyen & Kyaw Ze Ya Maung & Debora A. Ca, 2022. "Germline mutations in mitochondrial complex I reveal genetic and targetable vulnerability in IDH1-mutant acute myeloid leukaemia," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    6. Karl K. Krull & Syed Azmal Ali & Jeroen Krijgsveld, 2024. "Enhanced feature matching in single-cell proteomics characterizes IFN-γ response and co-existence of cell states," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    7. Nadege Gitego & Bogos Agianian & Oi Wei Mak & Vasantha Kumar MV & Emily H. Cheng & Evripidis Gavathiotis, 2023. "Chemical modulation of cytosolic BAX homodimer potentiates BAX activation and apoptosis," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    8. Manish Kumar & David Molkentine & Jessica Molkentine & Kathleen Bridges & Tongxin Xie & Liangpeng Yang & Andrew Hefner & Meng Gao & Reshub Bahri & Annika Dhawan & Mitchell J. Frederick & Sahil Seth & , 2021. "Inhibition of histone acetyltransferase function radiosensitizes CREBBP/EP300 mutants via repression of homologous recombination, potentially targeting a gain of function," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    9. Laura Lorenzo-Sanz & Marta Lopez-Cerda & Victoria da Silva-Diz & Marta H. Artés & Sandra Llop & Rosa M. Penin & Josep Oriol Bermejo & Eva Gonzalez-Suarez & Manel Esteller & Francesc Viñals & Enrique E, 2024. "Cancer cell plasticity defines response to immunotherapy in cutaneous squamous cell carcinoma," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    10. 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.
    11. Feng Wang & Yang Xu & Robert Wang & Beatrice Zhang & Noah Smith & Amber Notaro & Samantha Gaerlan & Eric Kutschera & Kathryn E. Kadash-Edmondson & Yi Xing & Lan Lin, 2023. "TEQUILA-seq: a versatile and low-cost method for targeted long-read RNA sequencing," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    12. Miquel Anglada-Girotto & Ludovica Ciampi & Sophie Bonnal & Sarah A. Head & Samuel Miravet-Verde & Luis Serrano, 2024. "In silico RNA isoform screening to identify potential cancer driver exons with therapeutic applications," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    13. Peter Bailey & Rachel A. Ridgway & Patrizia Cammareri & Mairi Treanor-Taylor & Ulla-Maja Bailey & Christina Schoenherr & Max Bone & Daniel Schreyer & Karin Purdie & Jason Thomson & William Rickaby & R, 2023. "Driver gene combinations dictate cutaneous squamous cell carcinoma disease continuum progression," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    14. Jiang-jiang Li & Tiantian Yu & Peiting Zeng & Jingyu Tian & Panpan Liu & Shuang Qiao & Shijun Wen & Yumin Hu & Qiao Liu & Wenhua Lu & Hui Zhang & Peng Huang, 2024. "Wild-type IDH2 is a therapeutic target for triple-negative breast cancer," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    15. Xiaojian Shi & Bryn Reinstadler & Hardik Shah & Tsz-Leung To & Katie Byrne & Luanna Summer & Sarah E. Calvo & Olga Goldberger & John G. Doench & Vamsi K. Mootha & Hongying Shen, 2022. "Combinatorial GxGxE CRISPR screen identifies SLC25A39 in mitochondrial glutathione transport linking iron homeostasis to OXPHOS," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    16. Fei Li & Yizhe Wang & Inah Hwang & Ja-Young Jang & Libo Xu & Zhong Deng & Eun Young Yu & Yiming Cai & Caizhi Wu & Zhenbo Han & Yu-Han Huang & Xiangao Huang & Ling Zhang & Jun Yao & Neal F. Lue & Paul , 2023. "Histone demethylase KDM2A is a selective vulnerability of cancers relying on alternative telomere maintenance," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    17. Yael Aylon & Noa Furth & Giuseppe Mallel & Gilgi Friedlander & Nishanth Belugali Nataraj & Meng Dong & Ori Hassin & Rawan Zoabi & Benjamin Cohen & Vanessa Drendel & Tomer Meir Salame & Saptaparna Mukh, 2022. "Breast cancer plasticity is restricted by a LATS1-NCOR1 repressive axis," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    18. Yanli Liu & Zhong Wu & Jin Zhou & Dinesh K. A. Ramadurai & Katelyn L. Mortenson & Estrella Aguilera-Jimenez & Yifei Yan & Xiaojun Yang & Alison M. Taylor & Katherine E. Varley & Jason Gertz & Peter S., 2021. "A predominant enhancer co-amplified with the SOX2 oncogene is necessary and sufficient for its expression in squamous cancer," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    19. Miao Yan & Qing Chen & Tianyi Liu & Xiaofeng Li & Peng Pei & Lei Zhou & Shan Zhou & Runhao Zhang & Kang Liang & Jian Dong & Xunbin Wei & Jinqiang Wang & Osamu Terasaki & Pu Chen & Zhen Gu & Libo Jiang, 2023. "Site-selective superassembly of biomimetic nanorobots enabling deep penetration into tumor with stiff stroma," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    20. Cécile Thirant & Agathe Peltier & Simon Durand & Amira Kramdi & Caroline Louis-Brennetot & Cécile Pierre-Eugène & Margot Gautier & Ana Costa & Amandine Grelier & Sakina Zaïdi & Nadège Gruel & Irène Ji, 2023. "Reversible transitions between noradrenergic and mesenchymal tumor identities define cell plasticity in neuroblastoma," Nature Communications, Nature, vol. 14(1), pages 1-18, 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:14:y:2023:i:1:d:10.1038_s41467-023-42748-8. 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.