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Cell, Tumor, and Stem Cell Biology |
1 Department of Pathology and Laboratory Medicine, Department of Biochemistry and Molecular Biology and Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina and 2 Departments of Urology and Pathology, Herbert Irving Comprehensive Cancer Center, Columbia University, College of Physicians and Surgeons, New York, New York
Requests for reprints: Dennis K. Watson, Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC 29425. Phone: 843-792-3962; Fax: 843-792-3940; E-mail: Watsondk{at}musc.edu.
Cell migration and invasion are critical events during the progression to metastasis. Without motile function, cancer cells are unable to leave the primary tumor site, invade through the basement membrane, and form secondary tumors. Expression of the epithelial-specific ETS factor prostate-derived ETS factor (PDEF) is reduced in human invasive breast tissue and lost in invasive breast cancer cell lines. Gain-of-function studies that examine different aspects of cell migration show that constitutive or inducible PDEF reexpression inhibits migration and invasion in multiple breast cancer cell lines, and loss-of-function studies show a stimulation of migration in noninvasive breast cancer cells. Furthermore, the introduction of PDEF into invasive breast cancer cells led to a remodeling of the actin cytoskeleton and altered focal adhesion localization and adherence levels. Cells expressing PDEF no longer form the defined morphologic polarity required for efficient, directional migration. Collectively, these data indicate that PDEF down-regulation in invasive breast cancer may promote actin-mediated cell migration through the extracellular matrix. [Cancer Res 2007;67(4):161825]
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D. P. Turner, V. J. Findlay, A. D. Kirven, O. Moussa, and D. K. Watson Global Gene Expression Analysis Identifies PDEF Transcriptional Networks Regulating Cell Migration during Cancer Progression Mol. Biol. Cell, September 1, 2008; 19(9): 3745 - 3757. [Abstract] [Full Text] [PDF] |
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