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

Autor: Crosas-Molist E; Barts Cancer Institute, Queen Mary University of London, John Vane Science Building, Charterhouse Square, London, EC1M 6BQ, UK.; Randall Centre for Cell and Molecular Biophysics, New Hunt's House, Guy's Campus, King's College London, London, SE1 1UL, UK., Graziani V; Barts Cancer Institute, Queen Mary University of London, John Vane Science Building, Charterhouse Square, London, EC1M 6BQ, UK.; Randall Centre for Cell and Molecular Biophysics, New Hunt's House, Guy's Campus, King's College London, London, SE1 1UL, UK., Maiques O; Barts Cancer Institute, Queen Mary University of London, John Vane Science Building, Charterhouse Square, London, EC1M 6BQ, UK.; Randall Centre for Cell and Molecular Biophysics, New Hunt's House, Guy's Campus, King's College London, London, SE1 1UL, UK., Pandya P; Randall Centre for Cell and Molecular Biophysics, New Hunt's House, Guy's Campus, King's College London, London, SE1 1UL, UK., Monger J; Barts Cancer Institute, Queen Mary University of London, John Vane Science Building, Charterhouse Square, London, EC1M 6BQ, UK., Samain R; Barts Cancer Institute, Queen Mary University of London, John Vane Science Building, Charterhouse Square, London, EC1M 6BQ, UK., George SL; Barts Cancer Institute, Queen Mary University of London, John Vane Science Building, Charterhouse Square, London, EC1M 6BQ, UK., Malik S; Randall Centre for Cell and Molecular Biophysics, New Hunt's House, Guy's Campus, King's College London, London, SE1 1UL, UK., Salise J; Randall Centre for Cell and Molecular Biophysics, New Hunt's House, Guy's Campus, King's College London, London, SE1 1UL, UK.; Centre for Biomolecular Spectroscopy, King's College London, London, SE1 1UL, UK., Morales V; Barts Cancer Institute, Queen Mary University of London, John Vane Science Building, Charterhouse Square, London, EC1M 6BQ, UK., Le Guennec A; Randall Centre for Cell and Molecular Biophysics, New Hunt's House, Guy's Campus, King's College London, London, SE1 1UL, UK.; Centre for Biomolecular Spectroscopy, King's College London, London, SE1 1UL, UK., Atkinson RA; Randall Centre for Cell and Molecular Biophysics, New Hunt's House, Guy's Campus, King's College London, London, SE1 1UL, UK.; Centre for Biomolecular Spectroscopy, King's College London, London, SE1 1UL, UK.; Institut de Pharmacologie et de Biologie Structurale (IPBS), UMR5089, CNRS-Université de Toulouse III-Paul Sabatier, BP 64182, 31077, Toulouse, Cedex 4, France., Marti RM; Department of Dermatology, Hospital Universitari Arnau de Vilanova, University of Lleida, CIBERONC, IRB Lleida, Lleida, 25198, Spain., Matias-Guiu X; Department of Pathology and Molecular Genetics, Hospital Universitari Arnau de Vilanova, University of Lleida, IRB Lleida, CIBERONC, Lleida, 25198, Spain.; Department of Pathology, Hospital Universitari de Bellvitge, University of Barcelona, IDIBELL, CIBERONC, L'Hospitalet de Llobregat, Barcelona, 08907, Spain., Charras G; London Centre for Nanotechnology, University College London, London, WC1H 0AH, UK.; Department of Cell and Developmental Biology, University College London, London, WC1E 6BT, UK., Conte MR; Randall Centre for Cell and Molecular Biophysics, New Hunt's House, Guy's Campus, King's College London, London, SE1 1UL, UK.; Centre for Biomolecular Spectroscopy, King's College London, London, SE1 1UL, UK., Elosegui-Artola A; Cell and Tissue Mechanobiology Lab, The Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK.; Department of Physics, King's College London, London, WC2R 2LS, UK., Holt M; Randall Centre for Cell and Molecular Biophysics, New Hunt's House, Guy's Campus, King's College London, London, SE1 1UL, UK.; School of Cardiovascular and Metabolic Medicine & Sciences, King's College London BHF Centre of Research Excellence, London, SE1 1UL, UK., Sanz-Moreno V; Barts Cancer Institute, Queen Mary University of London, John Vane Science Building, Charterhouse Square, London, EC1M 6BQ, UK. v.sanz-moreno@qmul.ac.uk.; Randall Centre for Cell and Molecular Biophysics, New Hunt's House, Guy's Campus, King's College London, London, SE1 1UL, UK. v.sanz-moreno@qmul.ac.uk.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 May 22; Vol. 14 (1), pp. 2740. Date of Electronic Publication: 2023 May 22.
DOI: 10.1038/s41467-023-38292-0
Abstrakt: 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
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