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Acute compressive stress activates RHO/ROCK-mediated cellular processes.

Sarah T Boyle1, Jasreen Kular1, Max Nobis2

  • 1Centre for Cancer Biology, SA Pathology and University of South Australia , Adelaide, South Australia, Australia.

Small Gtpases
|February 20, 2018
PubMed
Summary
This summary is machine-generated.

Acute compressive force activates RHOA and ROCK signaling, increasing actomyosin contractility and cell proliferation. This suggests compressive stress disrupts cellular homeostasis, impacting diseases like cancer.

Keywords:
RHOAROCKactomyosin tensioncompressive stresscytoskeletonextracellular matrix (ECM)mechanical signalingmechano-reciprocity

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Area of Science:

  • Cell biology
  • Mechanobiology
  • Biophysics

Background:

  • Cellular homeostasis relies on responding to external forces via mechanotransduction pathways.
  • Actomyosin cytoskeleton remodeling and tension are key to counterbalancing forces.
  • While extracellular matrix tension is well-studied, acute compressive force effects are less understood.

Purpose of the Study:

  • To investigate the impact of acute compressive force on cellular and tissue mechanics.
  • To elucidate the molecular pathways involved in the cellular response to compression.

Main Methods:

  • Application of acute compressive force to cells and tissues in a 3D context.
  • Measurement of RHOA-GTP levels, myosin phosphorylation, and actomyosin contractility.
  • Pharmacological inhibition of ROCK pathway.

Main Results:

  • Acute compressive force elevated RHOA-GTP levels and increased myosin phosphorylation and actomyosin contractility via ROCK.
  • Compression led to increased cell proliferation and expression of epithelial-mesenchymal transition regulators.
  • ROCK inhibition reduced myosin phosphorylation but not RHOA activation.

Conclusions:

  • Acute compressive stress disrupts cellular homeostasis through a RHO/ROCK-dependent mechanism.
  • Findings have implications for understanding diseases characterized by altered mechanical stress, such as cancer.