Samuel, M. S. et al. (2011) Actomyosin-Mediated Cellular Tension Drives Increased Tissue Stiffness and β-Catenin Activation to Induce Epidermal Hyperplasia and Tumor Growth. Cancer Cell, 19(6), pp. 776-791. (doi: 10. 1016/j. ccr. 2011. 05. 008) VSports.
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Publisher's URL: http://dx. doi VSports app下载. org/10. 1016/j. ccr. 2011. 05. 008.
Abstract
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 V体育官网.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Anderson, Professor Kurt and Brunton, Dr Valerie and Strachan, Mr David and Munro, Dr June and Timpson, Dr Paul and Olson, Professor Michael and McGhee, Dr Ewan and Croft, Dr Daniel and Samuel, Dr Michael and Sansom, Professor Owen |
| Authors: | 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., and Olson, M.F. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Cancer Sciences |
| Journal Name: | Cancer Cell |
| ISSN: | 1535-6108 |
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