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https://hdl.handle.net/2440/82328
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Type: | Journal article |
Title: | Actomyosin-mediated cellular tension drives increased tissue stiffness and B-catenin activation to induce interfollicular epidermal hyperplasia and tumor growth |
Author: | Samuel, M. Lopez, J. McGhee, E. Croft, D. Strachan, D. Timpson, P. Munro, J. Schroder, E. Zhou, J. Brunton, V. Barker, N. Clevers, H. Sansom, O. Anderson, K. Weaver, V. Olson, M. |
Citation: | Cancer Cell, 2011; 19(6):776-791 |
Publisher: | Cell Press |
Issue Date: | 2011 |
ISSN: | 1535-6108 1878-3686 |
Statement of Responsibility: | Michael S. Samuel, Jose I. Lopez, Ewan J. McGhee, Daniel R. Croft, David Strachan, Paul Timpson, June Munro, Ewald Schröder, Jing Zhou, Valerie G. Brunton, Nick Barker, Hans Clevers, Owen J. Sansom, Kurt I. Anderson, Valerie M. Weaver, and Michael F. Olson |
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. β-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: | Epidermis Cells, Cultured Animals Humans Mice Papilloma Skin Neoplasms Hyperplasia Actomyosin Signal Transduction Cell Proliferation beta Catenin rho-Associated Kinases Biomechanical Phenomena |
Rights: | © 2011 Elsevier Inc. |
DOI: | 10.1016/j.ccr.2011.05.008 |
Published version: | http://dx.doi.org/10.1016/j.ccr.2011.05.008 |
Appears in Collections: | Aurora harvest Molecular and Biomedical Science publications |
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