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Sp1 Is Required for Transforming Growth Factor-ß–Induced Mesenchymal Transition and Migration in Pancreatic Cancer Cells

¹ Department of Gastroenterology, University of Ulm, Ulm, Germany and ² Department of Internal Medicine, Division of Gastroenterology and Endocrinology, University of Marburg, Marburg, Germany

Requests for reprints: Volker Ellenrieder, Division of Gastroenterology and Endocrinology, University of Marburg, Baldinger Strasse, 35043 Marburg, Germany. Phone: 49-6421-28-66460; Fax: 49-6421-28-68922; E-mail: ellenrie{at}med.uni-marburg.de.

Transition from a sessile epithelial phenotype to a migrating mesenchymal phenotype is a crucial step in transforming growth factor-ß (TGF-ß)–induced pancreatic cancer cell migration and invasion. These profound morphologic and functional alterations are associated with characteristic changes in TGF-ß–regulated gene expression, defined by rapid repression of epithelial markers and a strong and sustained transcriptional induction of mesenchymal markers such as the intermediate filament vimentin. In this study, we have analyzed the role of the transcription factor Sp1 in TGF-ß–induced and Smad-mediated gene regulation during epithelial to mesenchymal transition (EMT) and migration of pancreatic cancer cells. Here, we show that Sp1 is required for TGF-ß–induced EMT, and that this function is especially mediated through transcriptional induction of vimentin. Our results emphasize the functional relevance of vimentin in TGF-ß–induced EMT because prevention of its induction strongly reduces cell migration. Altogether, this study helps to better understand the role of Sp1 in TGF-ß–induced progression of pancreatic cancer. It suggests that Sp1, via transcriptional induction of vimentin, cooperates with activated Smad complexes in mesenchymal transition and migration of pancreatic cancer cells upon TGF-ß stimulation. [Cancer Res 2007;67(4):1563–70]

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