This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Spaderna, S. Articles by Brabletz, T. Search for Related Content PubMed PubMed Citation Articles by Spaderna, S. Articles by Brabletz, T.

The Transcriptional Repressor ZEB1 Promotes Metastasis and Loss of Cell Polarity in Cancer

¹ Department of Visceral Surgery, University of Freiburg, Freiburg, Germany; ² Department of Pathology and ³ Nikolaus-Fiebiger-Center, University of Erlangen, Erlangen, Germany; ⁴ Max F. Perutz Laboratories, Medical University Vienna, Vienna, Austria; ⁵ Department of Pathology, University of Munchen, Munich, Germany; and ⁶ First Department of Internal Medicine, University of Mainz, Mainz, Germany

Requests for reprints: Thomas Brabletz, Department of Visceral Surgery, University of Freiburg, Hugstetter Str. 55, 79106 Freiburg, Germany. Phone: 49-0761270-2577; Fax: 49-0761270-2779; E-mail: thomas.brabletz{at}uniklinik-freiburg.de.

Invasion and metastasis are the hallmarks of malignant tumor progression and the main cause of death in cancer. The embryonic program "epithelial-mesenchymal transition" (EMT) is thought to trigger invasion by allowing tumor cell dissemination. Here, we describe that the EMT-inducing transcriptional repressor ZEB1 promotes colorectal cancer cell metastasis and loss of cell polarity. Thereby, ZEB1 suppresses the expression of cell polarity factors, in particular of Lgl2, which we found reduced in colorectal and breast cancers. We further show that retention of Lgl2 expression is critical for the epithelial phenotype and that its loss might be involved in metastasis. Thus, by linking EMT, loss of polarity, and metastasis, ZEB1 is a crucial promoter of malignant tumor progression. [Cancer Res 2008;68(2):537–44]

This article has been cited by other articles:

				Y. Li, T. G. VandenBoom II, D. Kong, Z. Wang, S. Ali, P. A. Philip, and F. H. Sarkar Up-regulation of miR-200 and let-7 by Natural Agents Leads to the Reversal of Epithelial-to-Mesenchymal Transition in Gemcitabine-Resistant Pancreatic Cancer Cells Cancer Res., August 15, 2009; 69(16): 6704 - 6712. [Abstract] [Full Text] [PDF]

				T. Arumugam, V. Ramachandran, K. F. Fournier, H. Wang, L. Marquis, J. L. Abbruzzese, G. E. Gallick, C. D. Logsdon, D. J. McConkey, and W. Choi Epithelial to Mesenchymal Transition Contributes to Drug Resistance in Pancreatic Cancer Cancer Res., July 15, 2009; 69(14): 5820 - 5828. [Abstract] [Full Text] [PDF]

				J. M. Drake, G. Strohbehn, T. B. Bair, J. G. Moreland, and M. D. Henry ZEB1 Enhances Transendothelial Migration and Represses the Epithelial Phenotype of Prostate Cancer Cells Mol. Biol. Cell, April 15, 2009; 20(8): 2207 - 2217. [Abstract] [Full Text] [PDF]

				V. R. Sobrado, G. Moreno-Bueno, E. Cubillo, L. J. Holt, M. A. Nieto, F. Portillo, and A. Cano The class I bHLH factors E2-2A and E2-2B regulate EMT J. Cell Sci., April 1, 2009; 122(7): 1014 - 1024. [Abstract] [Full Text] [PDF]

				T. Inuzuka, M. Tsuda, S. Tanaka, H. Kawaguchi, Y. Higashi, and Y. Ohba Integral Role of Transcription Factor 8 in the Negative Regulation of Tumor Angiogenesis Cancer Res., February 15, 2009; 69(4): 1678 - 1684. [Abstract] [Full Text] [PDF]

				C. P. Bracken, P. A. Gregory, N. Kolesnikoff, A. G. Bert, J. Wang, M. F. Shannon, and G. J. Goodall A Double-Negative Feedback Loop between ZEB1-SIP1 and the microRNA-200 Family Regulates Epithelial-Mesenchymal Transition Cancer Res., October 1, 2008; 68(19): 7846 - 7854. [Abstract] [Full Text] [PDF]