Document Detail

EGR1 and the ERK-ERF axis drive mammary cell migration in response to EGF.
MedLine Citation:
PMID:  22198386     Owner:  NLM     Status:  MEDLINE    
The signaling pathways that commit cells to migration are incompletely understood. We employed human mammary cells and two stimuli: epidermal growth factor (EGF), which induced cellular migration, and serum factors, which stimulated cell growth. In addition to strong activation of ERK by EGF, and AKT by serum, early transcription remarkably differed: while EGF induced early growth response-1 (EGR1), and this was required for migration, serum induced c-Fos and FosB to enhance proliferation. We demonstrate that induction of EGR1 involves ERK-mediated down-regulation of microRNA-191 and phosphorylation of the ETS2 repressor factor (ERF) repressor, which subsequently leaves the nucleus. Unexpectedly, knockdown of ERF inhibited migration, which implies migratory roles for exported ERF molecules. On the other hand, chromatin immunoprecipitation identified a subset of direct EGR1 targets, including EGR1 autostimulation and SERPINB2, whose transcription is essential for EGF-induced cell migration. In summary, EGR1 and the EGF-ERK-ERF axis emerge from our study as major drivers of growth factor-induced mammary cell migration.
Gabi Tarcic; Roi Avraham; Gur Pines; Ido Amit; Tal Shay; Yiling Lu; Yaara Zwang; Menachem Katz; Nir Ben-Chetrit; Jasmine Jacob-Hirsch; Laura Virgilio; Gideon Rechavi; George Mavrothalassitis; Gordon B Mills; Eytan Domany; Yosef Yarden
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-12-23
Journal Detail:
Title:  FASEB journal : official publication of the Federation of American Societies for Experimental Biology     Volume:  26     ISSN:  1530-6860     ISO Abbreviation:  FASEB J.     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-04-02     Completed Date:  2012-05-31     Revised Date:  2014-04-18    
Medline Journal Info:
Nlm Unique ID:  8804484     Medline TA:  FASEB J     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1582-92     Citation Subset:  IM    
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MeSH Terms
Cell Line
Cell Movement / drug effects*
Cell Proliferation / drug effects
Early Growth Response Protein 1 / genetics,  metabolism*
Epidermal Growth Factor / pharmacology*
Extracellular Signal-Regulated MAP Kinases / metabolism*
Gene Expression Profiling
Mammary Glands, Human / cytology*
MicroRNAs / genetics,  metabolism
Microarray Analysis
Proteome / analysis
Repressor Proteins / genetics,  metabolism*
Signal Transduction / drug effects*,  physiology
Two-Hybrid System Techniques
Grant Support
CA072981/CA/NCI NIH HHS; CA120248-01/CA/NCI NIH HHS; CA121994-01/CA/NCI NIH HHS; P30 CA016672/CA/NCI NIH HHS
Reg. No./Substance:
0/EGR1 protein, human; 0/ERF protein, human; 0/Early Growth Response Protein 1; 0/MIRN191 microRNA, human; 0/MicroRNAs; 0/Proteome; 0/Repressor Proteins; 62229-50-9/Epidermal Growth Factor; EC Signal-Regulated MAP Kinases
Comment In:
Cell Adh Migr. 2013 Jan-Feb;7(1):33-7   [PMID:  23076209 ]

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