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Actomyosin-Mediated Cellular Tension Drives Increased Tissue Stiffness and β-Catenin Activation to Induce Epidermal Hyperplasia and Tumor Growth
Open accessAbstract
SUMMARY 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.
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Cites
Tissue Cells Feel and Respond to the Stiffness of Their Substrate
Discher, D. E., Janmey, P., & Wang, Y.-L. (2005) · Science · doi:10.1126/science.1116995 · Cited by 6,382
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Self-citationActivation of the mouse cellular Harvey-ras gene in chemically induced benign skin papillomas
Balmain, A., Ramsden, M., Bowden, G. T., & Smith, J. (1984) · Nature · doi:10.1038/307658a0 · Cited by 529
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Mechanobiology of YAP and TAZ in physiology and disease
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Actin Dynamics, Architecture, and Mechanics in Cell Motility
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Promotion of Hepatocellular Carcinoma by the Intestinal Microbiota and TLR4
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Metadata
- 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., & Olson, M. F.
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2011-06
- Volume
- 19
- Issue
- 6
- Pages
- 776-791
- ISSN
- 1535-6108 (ISSN-L)
- OpenAlex
- W2086336177
- Cited by
- 541
- References
- 5
- FWCI
- 15.66
- Type
- journal article
- Language
- en
- Open access
- bronze
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- 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. https://doi.org/10.1016/j.ccr.2011.05.008
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
