Document Detail


Neuregulin 1-activated ERBB4 interacts with YAP to induce Hippo pathway target genes and promote cell migration.
MedLine Citation:
PMID:  25492965     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
The receptor tyrosine kinase ERBB4, a member of the epidermal growth factor receptor (EGFR) family, is unusual in that ERBB4 can undergo intramembrane proteolysis, releasing a soluble intracellular domain (ICD) that modulates transcription in the nucleus. We found that ERBB4 activated the transcriptional coactivator YAP, which promotes organ and tissue growth and is inhibited by the Hippo tumor-suppressor pathway. Overexpressing ERBB4 in cultured mammary epithelial cells or adding the ERBB4 ligand neuregulin 1 (NRG1) to breast cancer cell cultures promoted the expression of genes regulated by YAP, such as CTGF. Knocking down YAP or ERBB4 prevented the induction of CTGF expression by NRG1, as did treating cells with the ERBB inhibitors lapatinib or erlotinib, which reduced ERBB4 cleavage. NRG1 stimulated YAP activity to an extent comparable to that of EGF (epidermal growth factor) or LPA (lysophosphatidic acid), known activators of YAP. NRG1 stimulated YAP-dependent cell migration in breast cancer cell lines. These observations connect the unusual nuclear function of a growth factor receptor with a mechanosensory pathway and suggest that NRG1-ERBB4-YAP signaling contributes to the aggressive behavior of tumor cells.
Authors:
Jonathan W Haskins; Don X Nguyen; David F Stern
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Publication Detail:
Type:  Journal Article     Date:  2014-12-09
Journal Detail:
Title:  Science signaling     Volume:  7     ISSN:  1937-9145     ISO Abbreviation:  Sci Signal     Publication Date:  2014  
Date Detail:
Created Date:  2014-12-10     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101465400     Medline TA:  Sci Signal     Country:  United States    
Other Details:
Languages:  eng     Pagination:  ra116     Citation Subset:  IM    
Copyright Information:
Copyright © 2014, American Association for the Advancement of Science.
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