Acute compressive stress activates RHO/ROCK-mediated cellular processes

The ability to rapidly respond to applied force underpins cell/tissue homeostasis. This response is mediated by mechanotransduction pathways that regulate remodeling and tension of the actomyosin cytoskeleton to counterbalance external forces. Enhanced extracellular matrix tension hyper-activates me...

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Vydáno v:Small GTPases Ročník 11; číslo 5; s. 354 - 370
Hlavní autoři: Boyle, Sarah T., Kular, Jasreen, Nobis, Max, Ruszkiewicz, Andrew, Timpson, Paul, Samuel, Michael S.
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States Taylor & Francis 02.09.2020
Témata:
actomyosin tension
compressive stress
cytoskeleton
extracellular matrix (ECM)
mechanical signaling
mechano-reciprocity
Research Paper/Report
RHOA
ROCK
mechano-reciprocity
extracellular matrix (ECM)
ROCK
actomyosin tension
cytoskeleton
compressive stress
mechanical signaling
RHOA
ISSN:2154-1248, 2154-1256, 2154-1256
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Shrnutí:The ability to rapidly respond to applied force underpins cell/tissue homeostasis. This response is mediated by mechanotransduction pathways that regulate remodeling and tension of the actomyosin cytoskeleton to counterbalance external forces. Enhanced extracellular matrix tension hyper-activates mechanotransduction and characterizes diseased states such as cancer, but is also required for normal epidermal regeneration. While the impact of extracellular matrix tension on signaling and cell biology are well appreciated, that of acute compressive force is under-studied. We show here that acute compressive force applied to cells and tissues in a native 3-dimensional context elevates RHOA-GTP levels and increases regulatory myosin phosphorylation, actomyosin contractility and tension via ROCK. In consequence, cell proliferation was increased, as was the expression of regulators of epithelial-mesenchymal transition. Pharmacological inhibition of ROCK abrogated myosin phosphorylation, but not RHOA activation. Our results strongly suggest that acute compressive stress impairs cellular homeostasis in a RHO/ROCK-dependent manner, with implications for disease states such as cancer.
Bibliografie:ObjectType-Article-1
SourceType-Scholarly Journals-1
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ISSN:2154-1248
2154-1256
2154-1256
DOI:10.1080/21541248.2017.1413496