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Nat Cell Biol. 2017 Jun;19(6):724-731. doi: 10.1038/ncb3537. Epub 2017 May 29.

Linking E-cadherin mechanotransduction to cell metabolism through force-mediated activation of AMPK.

Author information

1
Department of Biochemistry, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA.
2
Interdisciplinary Graduate Program in Molecular and Cellular Biology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA.
3
Centre de Recherche en Cancérologie de Marseille, Aix Marseille University UM105, Institut Paoli Calmettes, UMR7258 CNRS, U1068 INSERM, Cell Polarity, Cell signalling and Cancer-Equipe labellisée Ligue Contre le Cancer, Marseille 13273, France.

Abstract

The response of cells to mechanical force is a major determinant of cell behaviour and is an energetically costly event. How cells derive energy to resist mechanical force is unknown. Here, we show that application of force to E-cadherin stimulates liver kinase B1 (LKB1) to activate AMP-activated protein kinase (AMPK), a master regulator of energy homeostasis. LKB1 recruits AMPK to the E-cadherin mechanotransduction complex, thereby stimulating actomyosin contractility, glucose uptake and ATP production. The increase in ATP provides energy to reinforce the adhesion complex and actin cytoskeleton so that the cell can resist physiological forces. Together, these findings reveal a paradigm for how mechanotransduction and metabolism are linked and provide a framework for understanding how diseases involving contractile and metabolic disturbances arise.

PMID:
28553939
PMCID:
PMC5494977
DOI:
10.1038/ncb3537
[Indexed for MEDLINE]
Free PMC Article

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