Extracellular Matrix Stiffness Controls VEGF Signaling and Processing in Endothelial Cells

2016 ◽  
Vol 231 (9) ◽  
pp. 2026-2039 ◽  
Author(s):  
Kelsey D. Sack ◽  
Madelane Teran ◽  
Matthew A. Nugent
Keyword(s):  
Extracellular Matrix ◽  
Endothelial Cells ◽  
Matrix Stiffness ◽  
Vegf Signaling ◽  
Extracellular Matrix Stiffness

scholarly journals Extracellular matrix stiffness modulates VEGF calcium signaling in endothelial cells: individual cell and population analysis

2015 ◽  
Vol 7 (9) ◽  
pp. 1011-1025 ◽  
Author(s):  
Kelsey E. Derricks ◽  
Vickery Trinkaus-Randall ◽  
Matthew A. Nugent
Keyword(s):  
Extracellular Matrix ◽  
Endothelial Cells ◽  
Endothelial Cell ◽  
Individual Cell ◽  
Population Analysis ◽  
Substrate Stiffness ◽  
Matrix Stiffness ◽  
Cell Responses ◽  
Signaling Dynamics ◽  
Extracellular Matrix Stiffness

Endothelial cell responses to VEGF are heterogeneous and vary with ECM stiffness. We analyzed individual cell responses to VEGF as a function of substrate stiffness to identify unique clusters of cell signaling dynamics.

Targeting extracellular matrix stiffness to attenuate disease: From molecular mechanisms to clinical trials

2018 ◽  
Vol 10 (422) ◽  
pp. eaao0475 ◽  
Author(s):  
Marsha C. Lampi ◽  
Cynthia A. Reinhart-King
Keyword(s):  
Extracellular Matrix ◽  
Clinical Trials ◽  
Cellular Response ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Therapeutic Interventions ◽  
Target Tissue ◽  
Matrix Stiffness ◽  
Extracellular Matrix Stiffness

Tissues stiffen during aging and during the pathological progression of cancer, fibrosis, and cardiovascular disease. Extracellular matrix stiffness is emerging as a prominent mechanical cue that precedes disease and drives its progression by altering cellular behaviors. Targeting extracellular matrix mechanics, by preventing or reversing tissue stiffening or interrupting the cellular response, is a therapeutic approach with clinical potential. Major drivers of changes to the mechanical properties of the extracellular matrix include phenotypically converted myofibroblasts, transforming growth factor β (TGFβ), and matrix cross-linking. Potential pharmacological interventions to overcome extracellular matrix stiffening are emerging clinically. Aside from targeting stiffening directly, alternative approaches to mitigate the effects of increased matrix stiffness aim to identify and inhibit the downstream cellular response to matrix stiffness. Therapeutic interventions that target tissue stiffening are discussed in the context of their limitations, preclinical drug development efforts, and clinical trials.

scholarly journals Functions of the Tumor Suppressors p53 and Rb in Actin Cytoskeleton Remodeling

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Takahiro Ebata ◽  
Hiroaki Hirata ◽  
Keiko Kawauchi
Keyword(s):  
Extracellular Matrix ◽  
Actin Cytoskeleton ◽  
Signaling Pathways ◽  
Cancer Progression ◽  
Tumor Suppressors ◽  
Retinoblastoma Protein ◽  
Matrix Stiffness ◽  
Extracellular Matrix Stiffness ◽  
Cytoskeleton Remodeling ◽  
Biochemical Signals

Mechanical microenvironments, such as extracellular matrix stiffness and strain, have crucial roles in cancer progression. Cells sense their microenvironments with mechanosensing biomolecules, which is accompanied by the modulation of actin cytoskeleton structures, and the signals are subsequently transduced downstream as biochemical signals. The tumor suppressors p53 and retinoblastoma protein (Rb) are known to prevent cancer progression. The p53 and Rb signaling pathways are disrupted in many types of cancers. Here, we review recent findings about the roles of these tumor suppressors in the regulation of mechanosensing biomolecules and the actin cytoskeleton. We further discuss how dysfunction in the p53- and/or Rb-mediated mechanosignaling pathways is potentially involved in cancer progression. These pathways might provide good targets for developing anticancer therapies.

scholarly journals A FAK-Cas-Rac-Lamellipodin Signaling Module Transduces Extracellular Matrix Stiffness into Mechanosensitive Cell Cycling

2014 ◽  
Vol 7 (330) ◽  
pp. ra57-ra57 ◽  
Author(s):  
Y. H. Bae ◽  
K. L. Mui ◽  
B. Y. Hsu ◽  
S.-L. Liu ◽  
A. Cretu ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Matrix Stiffness ◽  
Extracellular Matrix Stiffness ◽  
Cell Cycling
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