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...

Full description

Saved in:
Bibliographic Details
Published in:Small GTPases Vol. 11; no. 5; pp. 354 - 370
Main Authors: Boyle, Sarah T., Kular, Jasreen, Nobis, Max, Ruszkiewicz, Andrew, Timpson, Paul, Samuel, Michael S.
Format: Journal Article
Language:English
Published: United States Taylor & Francis 02.09.2020
Subjects:
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
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:2154-1248
2154-1256
2154-1256
DOI:10.1080/21541248.2017.1413496