ZEB1 turns into a transcriptional activator by interacting with YAP1 in aggressive cancer types.

Abstract:

:Early dissemination, metastasis and therapy resistance are central hallmarks of aggressive cancer types and the leading cause of cancer-associated deaths. The EMT-inducing transcriptional repressor ZEB1 is a crucial stimulator of these processes, particularly by coupling the activation of cellular motility with stemness and survival properties. ZEB1 expression is associated with aggressive behaviour in many tumour types, but the potent effects cannot be solely explained by its proven function as a transcriptional repressor of epithelial genes. Here we describe a direct interaction of ZEB1 with the Hippo pathway effector YAP, but notably not with its paralogue TAZ. In consequence, ZEB1 switches its function to a transcriptional co-activator of a 'common ZEB1/YAP target gene set', thereby linking two pathways with similar cancer promoting effects. This gene set is a predictor of poor survival, therapy resistance and increased metastatic risk in breast cancer, indicating the clinical relevance of our findings.

journal_name

Nat Commun

journal_title

Nature communications

authors

Lehmann W,Mossmann D,Kleemann J,Mock K,Meisinger C,Brummer T,Herr R,Brabletz S,Stemmler MP,Brabletz T

doi

10.1038/ncomms10498

subject

Has Abstract

pub_date

2016-02-15 00:00:00

pages

10498

issn

2041-1723

pii

ncomms10498

journal_volume

7

pub_type

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