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

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 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.

journal_name

Cancer Res

journal_title

Cancer research

authors

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

doi

10.1158/0008-5472.CAN-07-5682

subject

Has Abstract

pub_date

2008-01-15 00:00:00

pages

537-44

issue

2

eissn

0008-5472

issn

1538-7445

pii

68/2/537

journal_volume

68

pub_type

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