Actomyosin-Mediated Cellular Tension Drives Increased Tissue Stiffness and β-Catenin Activation to Induce Epidermal Hyperplasia and Tumor Growth
| Autor: | Daniel R. Croft, Michael F. Olson, Owen J. Sansom, Nick Barker, Paul Timpson, June Munro, Jose Lopez, Valerie M. Weaver, Michael S. Samuel, Hans Clevers, Valerie G. Brunton, Ewald Schroder, Ewan J. McGhee, David Strachan, Kurt I. Anderson, Jing Zhou |
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| Přispěvatelé: | Samuel, Michael S, Lopez, Jose I, McGhee, Ewan J, Croft, Daniel R, Strachan, David, Timpson, Paul, Munro, June, Schroder, Ewald, Zhou, Jing, Brunton, Valerie G, Barker, Nick, Clevers, Hans, Sansom, Owen J, Anderson, Kurt I, Weaver, Valerie M, Olson, Michael F, Hubrecht Institute for Developmental Biology and Stem Cell Research |
| Rok vydání: | 2011 |
| Předmět: |
Cancer Research
medicine.medical_specialty Skin Neoplasms Beta-catenin Myosin ATPase macromolecular substances Article Contractility epidermal hyerplasia Mice 03 medical and health sciences 0302 clinical medicine Internal medicine medicine Animals Humans ROCK2 Cells Cultured beta Catenin Tissue homeostasis Cell Proliferation 030304 developmental biology actomyosin-mediated cellular tension rho-Associated Kinases 0303 health sciences Hyperplasia Papilloma Mechanosensation biology beta-catenin Cell Biology Actomyosin Biomechanical Phenomena 3. Good health Cell biology tumor growth Endocrinology Oncology 030220 oncology & carcinogenesis Catenin biology.protein Epidermis Signal transduction Signal Transduction |
| Zdroj: | Samuel, M S, Lopez, J I, McGhee, E J, Croft, D R, Strachan, D, Timpson, P, Munro, J, Schröder, E, Zhou, J, Brunton, V G, Barker, N, Clevers, H, Sansom, O J, Anderson, K I, Weaver, V M & Olson, M F 2011, ' Actomyosin-mediated cellular tension drives increased tissue stiffness and β-catenin activation to induce epidermal hyperplasia and tumor growth ', Cancer Cell, vol. 19, no. 6, pp. 776-91 . https://doi.org/10.1016/j.ccr.2011.05.008 Cancer Cell, 19(6), 776-791. Cell Press |
| ISSN: | 1535-6108 |
| DOI: | 10.1016/j.ccr.2011.05.008 |
| Popis: | Tumors and associated stroma manifest mechanical properties that promote cancer. Mechanosensation of tissue stiffness activates the Rho/ROCK pathway to increase actomyosin-mediated cellular tension to re-establish force equilibrium. To determine how actomyosin tension affects tissue homeostasis and tumor development, we expressed conditionally active ROCK2 in mouse skin. ROCK activation elevated tissue stiffness via increased collagen. beta-catenin, a key element of mechanotranscription pathways, was stabilized by ROCK activation leading to nuclear accumulation, transcriptional activation, and consequent hyperproliferation and skin thickening. Inhibiting actomyosin contractility by blocking LIMK or myosin ATPase attenuated these responses, as did FAK inhibition. Tumor number, growth, and progression were increased by ROCK activation, while ROCK blockade was inhibitory, implicating actomyosin-mediated cellular tension and consequent collagen deposition as significant tumor promoters. [KEYWORDS: Actomyosin/ physiology, Animals, Biomechanics, Cell Proliferation, Cells, Cultured, Epidermis/ pathology, Humans, Hyperplasia, Mice, Papilloma/etiology, Signal Transduction, Skin Neoplasms/ etiology, beta Catenin/ physiology, rho-Associated Kinases/analysis/genetics/physiology] |
| Databáze: | OpenAIRE |
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