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https://hdl.handle.net/2440/80727
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Type: | Journal article |
Title: | Mechanotransduction pathways promoting tumor progression are activated in invasive human squamous cell carcinoma |
Author: | Ibbetson, S. Pyne, N. Pollard, A. Olson, M. Samuel, M. |
Citation: | American Journal of Pathology, 2013; 183(3):930-937 |
Publisher: | Amer Soc Investigative Pathology Inc |
Issue Date: | 2013 |
ISSN: | 0002-9440 1525-2191 |
Statement of Responsibility: | S. Jan Ibbetson, Natasha T. Pyne, Anthony N. Pollard, Michael F. Olson, and Michael S. Samuel |
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. |
Keywords: | Dermis Animals Humans Mice Carcinoma, Squamous Cell Skin Neoplasms Neoplasm Invasiveness Disease Models, Animal Disease Progression Collagen Glycogen Synthase Kinase 3 Fibronectins Cell Adhesion Molecules Integrins Fluorescent Antibody Technique Mechanotransduction, Cellular Enzyme Activation beta Catenin Focal Adhesion Protein-Tyrosine Kinases rho-Associated Kinases |
Rights: | Copyright © 2013 American Society for Investigative Pathology. |
DOI: | 10.1016/j.ajpath.2013.05.014 |
Published version: | http://dx.doi.org/10.1016/j.ajpath.2013.05.014 |
Appears in Collections: | Aurora harvest Molecular and Biomedical Science publications |
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