Ibbetson, S. J., Pyne, N. T., Pollard, A. N., Olson, M. F. and Samuel, M. S. (2013) Mechanotransduction pathways promoting tumor progression are activated in invasive human squamous cell carcinoma. American Journal of Pathology, 183(3), pp. 930-937. (doi: 10.1016/j.ajpath.2013.05.014) (PMID:23830873)
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Abstract
Cutaneous squamous cell carcinomas (SCCs) are commonly diagnosed skin cancers that may progress to invasiveness in the absence of early intervention. Using a murine model of SCC, we have previously demonstrated that activation of the Rho-associated kinase (ROCK) signaling pathway promotes rapid progression of pre-neoplastic lesions to invasive SCC. Herein we demonstrate that in human cutaneous SCC, ROCK signaling is increasingly up-regulated with tumor progression in both tumor cells and cells of the tumor microenvironment and is accompanied by key tumor-promoting changes in the extracellular matrix protein composition. The mechanotransduction pathway mediated by integrin signaling through FAK, GSK3β, and the transcription coactivator β-catenin is also progressively activated in human cutaneous SCC. Our observations indicate that ROCK activation is a tumor promoter in human cutaneous SCC and acts via mechanotransduction of signals to β-catenin. Our experiments raise the possibility that inhibition of ROCK signaling could be a useful therapeutic approach to halt cutaneous SCC progression by reducing the signal flux through this pathway to physiologic levels, thereby normalizing the extracellular matrix composition.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Olson, Professor Michael |
| Authors: | Ibbetson, S. J., Pyne, N. T., Pollard, A. N., Olson, M. F., and Samuel, M. S. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Cancer Sciences |
| Journal Name: | American Journal of Pathology |
| Publisher: | Elsevier |
| ISSN: | 0002-9440 |
| ISSN (Online): | 1525-2191 |
| Published Online: | 02 July 2013 |
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