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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
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    References listed on IDEAS

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