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

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 Atkinson; Rosa M Marti; Xavier Matias-Guiu; Guillaume Charras; Maria R Conte; Alberto Elosegui-Artola; Mark Holt; Victoria Sanz-Moreno

doi:10.1038/s41467-023-38292-0

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

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 Atkinson, Rosa M Marti, Xavier Matias-Guiu, Guillaume Charras, Maria R Conte, Alberto Elosegui-Artola, Mark Holt, Victoria Sanz-Moreno

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	2740
Journal	Nature Communications
Volume	14
Issue number	1
DOIs	https://doi.org/10.1038/s41467-023-38292-0 https://doi.org/10.1038/s41467-023-38292-0
Publication status	Published - 22 May 2023

Keywords

Humans
Adenosine Triphosphate/metabolism
AMP-Activated Protein Kinases/metabolism
Cell Adhesion
Cell Movement/physiology
Mitochondrial Dynamics
Myosin Type II/metabolism
Neoplasms
Oxidative Phosphorylation
Phosphorylation

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Crosas-Molist, E., Graziani, V., Maiques, O., Pandya, P., Monger, J., Samain, R., George, S. L., Malik, S., Salise, J., Morales, V., Le Guennec, A., Atkinson, R. A., Marti, R. M., Matias-Guiu, X., Charras, G., Conte, M. R., Elosegui-Artola, A., Holt, M., & Sanz-Moreno, V. (2023). AMPK is a mechano-metabolic sensor linking cell adhesion and mitochondrial dynamics to Myosin-dependent cell migration. Nature Communications, 14(1), 2740. https://doi.org/10.1038/s41467-023-38292-0, https://doi.org/10.1038/s41467-023-38292-0

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

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.",

keywords = "Humans, Adenosine Triphosphate/metabolism, AMP-Activated Protein Kinases/metabolism, Cell Adhesion, Cell Movement/physiology, Mitochondrial Dynamics, Myosin Type II/metabolism, Neoplasms, Oxidative Phosphorylation, Phosphorylation",

author = "Eva Crosas-Molist and Vittoria Graziani and Oscar Maiques and Pahini Pandya and Joanne Monger and Remi Samain and George, {Samantha L} and Saba Malik and Jerrine Salise and Valle Morales and {Le Guennec}, Adrien and Atkinson, {R Andrew} and Marti, {Rosa M} and Xavier Matias-Guiu and Guillaume Charras and Conte, {Maria R} and Alberto Elosegui-Artola and Mark Holt and Victoria Sanz-Moreno",

note = "{\textcopyright} 2023. The Author(s).",

year = "2023",

month = may,

day = "22",

doi = "10.1038/s41467-023-38292-0",

language = "English",

volume = "14",

pages = "2740",

journal = "Nature Communications",

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number = "1",

}

Crosas-Molist, E, Graziani, V, Maiques, O, Pandya, P, Monger, J, Samain, R, George, SL, Malik, S, Salise, J, Morales, V, Le Guennec, A , Atkinson, RA, Marti, RM, Matias-Guiu, X, Charras, G, Conte, MR , Elosegui-Artola, A , Holt, M & Sanz-Moreno, V 2023, 'AMPK is a mechano-metabolic sensor linking cell adhesion and mitochondrial dynamics to Myosin-dependent cell migration', Nature Communications, vol. 14, no. 1, pp. 2740. https://doi.org/10.1038/s41467-023-38292-0, https://doi.org/10.1038/s41467-023-38292-0

TY - JOUR

T1 - AMPK is a mechano-metabolic sensor linking cell adhesion and mitochondrial dynamics to Myosin-dependent cell migration

AU - Crosas-Molist, Eva

AU - Graziani, Vittoria

AU - Maiques, Oscar

AU - Pandya, Pahini

AU - Monger, Joanne

AU - Samain, Remi

AU - George, Samantha L

AU - Malik, Saba

AU - Salise, Jerrine

AU - Morales, Valle

AU - Le Guennec, Adrien

AU - Atkinson, R Andrew

AU - Marti, Rosa M

AU - Matias-Guiu, Xavier

AU - Charras, Guillaume

AU - Conte, Maria R

AU - Elosegui-Artola, Alberto

AU - Holt, Mark

AU - Sanz-Moreno, Victoria

PY - 2023/5/22

Y1 - 2023/5/22

N2 - 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.

AB - 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.

KW - Humans

KW - Adenosine Triphosphate/metabolism

KW - AMP-Activated Protein Kinases/metabolism

KW - Cell Adhesion

KW - Cell Movement/physiology

KW - Mitochondrial Dynamics

KW - Myosin Type II/metabolism

KW - Neoplasms

KW - Oxidative Phosphorylation

KW - Phosphorylation

U2 - 10.1038/s41467-023-38292-0

DO - 10.1038/s41467-023-38292-0

M3 - Article

C2 - 37217519

SN - 2041-1723

VL - 14

SP - 2740

JO - Nature Communications

JF - Nature Communications

IS - 1

ER -

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

Abstract

Keywords

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