The transcriptional repressor ZEB1 promotes metastasis and loss of cell polarity in cancer

S. Spaderna, O. Schmalhofer, M. Wahlbuhl, A. Dimmler, K. Bauer, A. Sultan, F. Hlubek, A. Jung, D. Strand, A. Eger, T. Kirchner, J. Behrens, T. Brabletz

Publikation: Beitrag in FachzeitschriftArtikelBegutachtung

Abstract

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 showthat 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. ©2008 American Association for Cancer Research.
OriginalspracheEnglisch
Seiten (von - bis)537-544
Seitenumfang8
FachzeitschriftCancer Research
Jahrgang68
Ausgabenummer2
DOIs
PublikationsstatusVeröffentlicht - 15 Jän. 2008

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