zeb1 in pancreatic cancerzeb1在胰腺癌.pdf

Cancers 2010, 2, 1617-1628; doi:10.3390/cancers2031617 OPEN ACCESS cancers ISSN 2072-6694 /journal/cancers Review ZEB1 in Pancreatic Cancer Ulrich Wellner, Thomas Brabletz and Tobias Keck * Department of General and Visceral Surgery, University of Freiburg, Hugstetter Straße 55, 79106 Freiburg, Germany; E-Mails: ulrich.wellner@uniklinik-freiburg.de (U.W.); thomas.brabletz@uniklinik-freiburg.de (T.B.) * Author to whom correspondence should be addressed; E-Mail: tobias.keck@uniklinik-freiburg.de; Tel.: +49-761-270-2808; Fax: +49-761-270-2808. Received: 30 June 2010; in revised form: 16 August 2010 / Accepted: 17 August 2010 / Published: 18 August 2010 Abstract: Pancreatic cancer is one of the most malignant human neoplasias. On the molecular level, epithelial-mesenchymal transition (EMT) has been demonstrated to contribute to the malignant phenotype of pancreatic cancer cells. ZEB1 is a transcriptional repressor that has been identified as an inducer of EMT. A negative feedback loop between ZEB1 and microRNA-200c has been shown to regulate this EMT induction in various models. With respect to pancreatic cancer, primary effects of EMT comprise increased local and distant tumor cell dissemination. Another recently described feature of the EMT is the acquisition of cancer stem cell traits. For pancreatic cancer cells, antagonism between ZEB1 and stemness-inhibiting micro-RNAs has been demonstrated to contribute to this