Mechano-reciprocity is maintained between physiological boundaries by tuning signal flux through the Rho-associated protein kinase
| Autor: | Sarah T. Boyle, Michael S. Samuel |
|---|---|
| Přispěvatelé: | Boyle, Sarah T, Samuel, Michael S |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
wound healing Biochemistry 14-3-3ζ MYPT Focal adhesion Extracellular matrix 03 medical and health sciences Paracrine signalling Rho fibroblasts Neoplasms ROCK cancer Animals Homeostasis Humans Molecular Targeted Therapy Mechanotransduction Cytoskeleton Rho-associated protein kinase mechanotransduction Mechanical Phenomena rho-Associated Kinases Mini-Reviews biology Wnt signaling pathway Cell Biology Cell biology 030104 developmental biology Mitogen-activated protein kinase extra-cellular matrix mechanoreciprocity biology.protein Signal Transduction |
| Zdroj: | Small GTPases. 7(3) |
| ISSN: | 2154-1256 |
| Popis: | The mechanical properties of the ECM strongly influence the behavior of all cell types within a given tissue. Increased matrix tension promotes epithelial cell proliferation by engaging mitogenic mechanotransduction signaling including the Salvador/Warts/Hippo, PI 3-kinase, Rho, Wnt and MAP kinase pathways. The Rho signaling pathways in particular are capable of increasing intra-cellular tension by elevating the production and contractility of the actomyosin cytoskeleton, which counteracts tension changes within the matrix in a process termed mechano-reciprocity. We have discovered that Rho-ROCK signaling increases the production of ECM through paracrine signaling between the epithelium and fibroblasts and also the remodeling of the ECM by regulating focal adhesion dynamics in fibroblasts. These two phenomena together cause increased ECM tension. Enhanced mechano-reciprocity results in ever-increasing intra- and extra-cellular tension in a vicious cycle that promotes cell proliferation and tumor progression. These insights reveal that inhibiting mechano-reciprocity, reducing ECM tension and targeting cancer-associated fibroblasts in a coordinated fashion has potential as cancer therapy. Refereed/Peer-reviewed |
| Databáze: | OpenAIRE |
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