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

被引：440

作者：

Spaderna, Simone ^{[1
]}

Schmalhofer, Otto ^{[1
]}

Wahlbuhl, Mandy ^{[2
]}

Dimmler, Arno ^{[2
]}

Bauer, Katja ^{[3
]}

Sultan, Aneesa ^{[4
]}

Hlubek, Falk ^{[5
]}

Jung, Andreas ^{[5
]}

Strand, Dennis ^{[6
]}

Eger, Andreas ^{[4
]}

Kirchner, Thomas ^{[5
]}

Behrens, Juergen ^{[3
]}

Brabletz, Thomas ^{[1
]}

机构：

[1] Univ Freiburg, Dept Visceral Surg, D-79106 Freiburg, Germany

[2] Univ Erlangen Nurnberg, Dept Pathol, Erlangen, Germany

[3] Univ Erlangen Nurnberg, Nikolaus Fiebiger Ctr, Erlangen, Germany

[4] Med Univ Vienna, Max F Perutz Labs, Vienna, Austria

[5] Univ Munich, Inst Pathol, D-8000 Munich, Germany

[6] Johannes Gutenberg Univ Mainz, Dept Internal Med 1, D-6500 Mainz, Germany

来源：

CANCER RESEARCH | 2008年 / 68卷 / 02期

关键词：

D O I：

10.1158/0008-5472.CAN-07-5682

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：537 / 544

页数：8

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