AMPK is a mechano-metabolic sensor linking cell adhesion and mitochondrial dynamics to Myosin-dependent cell migration.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
22 05 2023
22 05 2023
Historique:
received:
13
05
2022
accepted:
24
04
2023
medline:
24
5
2023
pubmed:
23
5
2023
entrez:
22
5
2023
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 37217519
doi: 10.1038/s41467-023-38292-0
pii: 10.1038/s41467-023-38292-0
pmc: PMC10202939
doi:
Substances chimiques
Adenosine Triphosphate
8L70Q75FXE
AMP-Activated Protein Kinases
EC 2.7.11.31
Myosin Type II
EC 3.6.1.-
PRKAB1 protein, human
EC 2.7.11.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2740Subventions
Organisme : British Heart Foundation
ID : IG/16/2/32273
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C33043/A12065
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C33043/A24478
Pays : United Kingdom
Organisme : Medical Research Council
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 202767/Z/16/Z
Pays : United Kingdom
Informations de copyright
© 2023. The Author(s).
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