IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-38292-0.html
   My bibliography  Save this article

AMPK is a mechano-metabolic sensor linking cell adhesion and mitochondrial dynamics to Myosin-dependent cell migration

Author

Listed:
  • Eva Crosas-Molist

    (Charterhouse Square
    Guy’s Campus, King’s College London)

  • Vittoria Graziani

    (Charterhouse Square
    Guy’s Campus, King’s College London)

  • Oscar Maiques

    (Charterhouse Square
    Guy’s Campus, King’s College London)

  • Pahini Pandya

    (Guy’s Campus, King’s College London)

  • Joanne Monger

    (Charterhouse Square)

  • Remi Samain

    (Charterhouse Square)

  • Samantha L. George

    (Charterhouse Square)

  • Saba Malik

    (Guy’s Campus, King’s College London)

  • Jerrine Salise

    (Guy’s Campus, King’s College London
    King’s College London)

  • Valle Morales

    (Charterhouse Square)

  • Adrien Le Guennec

    (Guy’s Campus, King’s College London
    King’s College London)

  • R. Andrew Atkinson

    (Guy’s Campus, King’s College London
    King’s College London
    UMR5089, CNRS-Université de Toulouse III-Paul Sabatier)

  • Rosa M. Marti

    (University of Lleida, CIBERONC, IRB Lleida)

  • Xavier Matias-Guiu

    (University of Lleida, IRB Lleida, CIBERONC
    IDIBELL, CIBERONC, L’Hospitalet de Llobregat)

  • Guillaume Charras

    (University College London
    University College London)

  • Maria R. Conte

    (Guy’s Campus, King’s College London
    King’s College London)

  • Alberto Elosegui-Artola

    (The Francis Crick Institute
    King’s College London)

  • Mark Holt

    (Guy’s Campus, King’s College London
    King’s College London BHF Centre of Research Excellence)

  • Victoria Sanz-Moreno

    (Charterhouse Square
    Guy’s Campus, King’s College London)

Abstract

Cell migration is crucial for cancer dissemination. We find that AMP-activated protein kinase (AMPK) controls cell migration by acting as an adhesion sensing molecular hub. In 3-dimensional matrices, fast-migrating amoeboid cancer cells exert low adhesion/low traction linked to low ATP/AMP, leading to AMPK activation. In turn, AMPK plays a dual role controlling mitochondrial dynamics and cytoskeletal remodelling. High AMPK activity in low adhering migratory cells, induces mitochondrial fission, resulting in lower oxidative phosphorylation and lower mitochondrial ATP. Concurrently, AMPK inactivates Myosin Phosphatase, increasing Myosin II-dependent amoeboid migration. Reducing adhesion or mitochondrial fusion or activating AMPK induces efficient rounded-amoeboid migration. AMPK inhibition suppresses metastatic potential of amoeboid cancer cells in vivo, while a mitochondrial/AMPK-driven switch is observed in regions of human tumours where amoeboid cells are disseminating. We unveil how mitochondrial dynamics control cell migration and suggest that AMPK is a mechano-metabolic sensor linking energetics and the cytoskeleton.

Suggested Citation

  • Eva Crosas-Molist & Vittoria Graziani & Oscar Maiques & Pahini Pandya & Joanne Monger & Remi Samain & Samantha L. George & Saba Malik & Jerrine Salise & Valle Morales & Adrien Le Guennec & R. Andrew A, 2023. "AMPK is a mechano-metabolic sensor linking cell adhesion and mitochondrial dynamics to Myosin-dependent cell migration," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38292-0
    DOI: 10.1038/s41467-023-38292-0
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-38292-0
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-38292-0?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. Andrew D. Doyle & Nicole Carvajal & Albert Jin & Kazue Matsumoto & Kenneth M. Yamada, 2015. "Local 3D matrix microenvironment regulates cell migration through spatiotemporal dynamics of contractility-dependent adhesions," Nature Communications, Nature, vol. 6(1), pages 1-15, December.
    2. Bing Xiao & Matthew J. Sanders & Elizabeth Underwood & Richard Heath & Faith V. Mayer & David Carmena & Chun Jing & Philip A. Walker & John F. Eccleston & Lesley F. Haire & Peter Saiu & Steven A. Howe, 2011. "Structure of mammalian AMPK and its regulation by ADP," Nature, Nature, vol. 472(7342), pages 230-233, April.
    3. Jin Suk Park & Christoph J. Burckhardt & Rossana Lazcano & Luisa M. Solis & Tadamoto Isogai & Linqing Li & Christopher S. Chen & Boning Gao & John D. Minna & Robert Bachoo & Ralph J. DeBerardinis & Ga, 2020. "Mechanical regulation of glycolysis via cytoskeleton architecture," Nature, Nature, vol. 578(7796), pages 621-626, February.
    4. Jose L. Orgaz & Pahini Pandya & Rimple Dalmeida & Panagiotis Karagiannis & Berta Sanchez-Laorden & Amaya Viros & Jean Albrengues & Frank O. Nestle & Anne J. Ridley & Cedric Gaggioli & Richard Marais &, 2014. "Diverse matrix metalloproteinase functions regulate cancer amoeboid migration," Nature Communications, Nature, vol. 5(1), pages 1-13, September.
    5. Yelena Y. Bernadskaya & Saahil Brahmbhatt & Stephanie E. Gline & Wei Wang & Lionel Christiaen, 2019. "Discoidin-domain receptor coordinates cell-matrix adhesion and collective polarity in migratory cardiopharyngeal progenitors," Nature Communications, Nature, vol. 10(1), pages 1-15, December.
    6. Edwin A. Clark & Todd R. Golub & Eric S. Lander & Richard O. Hynes, 2000. "Genomic analysis of metastasis reveals an essential role for RhoC," Nature, Nature, vol. 406(6795), pages 532-535, August.
    7. Edoardo Gaude & Christian Frezza, 2016. "Tissue-specific and convergent metabolic transformation of cancer correlates with metastatic potential and patient survival," Nature Communications, Nature, vol. 7(1), pages 1-9, December.
    8. Irene Rodriguez-Hernandez & Oscar Maiques & Leonie Kohlhammer & Gaia Cantelli & Anna Perdrix-Rosell & Joanne Monger & Bruce Fanshawe & Victoria L. Bridgeman & Sophia N. Karagiannis & Rosa M. Penin & J, 2020. "WNT11-FZD7-DAAM1 signalling supports tumour initiating abilities and melanoma amoeboid invasion," Nature Communications, Nature, vol. 11(1), pages 1-20, December.
    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. Camilla Tombari & Alessandro Zannini & Rebecca Bertolio & Silvia Pedretti & Matteo Audano & Luca Triboli & Valeria Cancila & Davide Vacca & Manuel Caputo & Sara Donzelli & Ilenia Segatto & Simone Vodr, 2023. "Mutant p53 sustains serine-glycine synthesis and essential amino acids intake promoting breast cancer growth," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    2. Danielle L. Schmitt & Stephanie D. Curtis & Anne C. Lyons & Jin-fan Zhang & Mingyuan Chen & Catherine Y. He & Sohum Mehta & Reuben J. Shaw & Jin Zhang, 2022. "Spatial regulation of AMPK signaling revealed by a sensitive kinase activity reporter," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    3. Richard J. Hewitt & Franz Puttur & David C. A. Gaboriau & Frédéric Fercoq & Maryline Fresquet & William J. Traves & Laura L. Yates & Simone A. Walker & Philip L. Molyneaux & Samuel V. Kemp & Andrew G., 2023. "Lung extracellular matrix modulates KRT5+ basal cell activity in pulmonary fibrosis," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    4. Akifumi Shiomi & Taikopaul Kaneko & Kaori Nishikawa & Arata Tsuchida & Takashi Isoshima & Mayuko Sato & Kiminori Toyooka & Kentaro Doi & Hidekazu Nishikii & Hirofumi Shintaku, 2024. "High-throughput mechanical phenotyping and transcriptomics of single cells," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    5. Shasha Yao & Yi Wang & Qian Tang & Yujie Yin & Yu Geng & Lei Xu & Shifu Liang & Jiajia Xiang & Jiaqi Fan & Jianbin Tang & Jian Liu & Shiqun Shao & Youqing Shen, 2024. "A plug-and-play monofunctional platform for targeted degradation of extracellular proteins and vesicles," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    6. Yi Zhang & Mingjie Wang & Ling Ye & Shengqi Shen & Yuxi Zhang & Xiaoyu Qian & Tong Zhang & Mengqiu Yuan & Zijian Ye & Jin Cai & Xiang Meng & Shiqiao Qiu & Shengzhi Liu & Rui Liu & Weidong Jia & Xianzh, 2024. "HKDC1 promotes tumor immune evasion in hepatocellular carcinoma by coupling cytoskeleton to STAT1 activation and PD-L1 expression," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    7. Yuechuan Lin & Nichaluk Leartprapun & Justin C. Luo & Steven G. Adie, 2022. "Light-sheet photonic force optical coherence elastography for high-throughput quantitative 3D micromechanical imaging," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    8. Giovanni Codacci-Pisanelli, 2017. "Epigenetic Targets in the Treatment of cancer," Novel Approaches in Drug Designing & Development, Juniper Publishers Inc., vol. 1(4), pages 56-57, June.
    9. Jia-Cheng Lu & Lei-Lei Wu & Yi-Ning Sun & Xiao-Yong Huang & Chao Gao & Xiao-Jun Guo & Hai-Ying Zeng & Xu-Dong Qu & Yi Chen & Dong Wu & Yan-Zi Pei & Xian-Long Meng & Yi-Min Zheng & Chen Liang & Peng-Fe, 2024. "Macro CD5L+ deteriorates CD8+T cells exhaustion and impairs combination of Gemcitabine-Oxaliplatin-Lenvatinib-anti-PD1 therapy in intrahepatic cholangiocarcinoma," Nature Communications, Nature, vol. 15(1), pages 1-23, December.
    10. Marco Sciacovelli & Aurelien Dugourd & Lorea Valcarcel Jimenez & Ming Yang & Efterpi Nikitopoulou & Ana S. H. Costa & Laura Tronci & Veronica Caraffini & Paulo Rodrigues & Christina Schmidt & Dylan Ge, 2022. "Dynamic partitioning of branched-chain amino acids-derived nitrogen supports renal cancer progression," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    11. Tea Pemovska & Johannes W. Bigenzahn & Ismet Srndic & Alexander Lercher & Andreas Bergthaler & Adrián César-Razquin & Felix Kartnig & Christoph Kornauth & Peter Valent & Philipp B. Staber & Giulio Sup, 2021. "Metabolic drug survey highlights cancer cell dependencies and vulnerabilities," Nature Communications, Nature, vol. 12(1), pages 1-19, December.
    12. Ashenafi Bulle & Peng Liu & Kuljeet Seehra & Sapana Bansod & Yali Chen & Kiran Zahra & Vikas Somani & Iftikhar Ali Khawar & Hung-Po Chen & Paarth B. Dodhiawala & Lin Li & Yutong Geng & Chia-Kuei Mo & , 2024. "Combined KRAS-MAPK pathway inhibitors and HER2-directed drug conjugate is efficacious in pancreatic cancer," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    13. Jorge Barbazan & Carlos Pérez-González & Manuel Gómez-González & Mathieu Dedenon & Sophie Richon & Ernest Latorre & Marco Serra & Pascale Mariani & Stéphanie Descroix & Pierre Sens & Xavier Trepat & D, 2023. "Cancer-associated fibroblasts actively compress cancer cells and modulate mechanotransduction," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    14. Sara G. Romeo & Ilaria Secco & Edoardo Schneider & Christina M. Reumiller & Celio X. C. Santos & Anna Zoccarato & Vishal Musale & Aman Pooni & Xiaoke Yin & Konstantinos Theofilatos & Silvia Cellone Tr, 2023. "Human blood vessel organoids reveal a critical role for CTGF in maintaining microvascular integrity," 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_s41467-023-38292-0. 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.