TY - JOUR
T1 - EGR1 and the ERK-ERF axis drive mammary cell migration in response to EGF
AU - Tarcic, Gabi
AU - Avraham, Roi
AU - Pines, Gur
AU - Amit, Ido
AU - Shay, Tal
AU - Lu, Yiling
AU - Zwang, Yaara
AU - Katz, Menachem
AU - Ben-Chetrit, Nir
AU - Jacob-Hirsch, Jasmine
AU - Virgilio, Laura
AU - Rechavi, Gideon
AU - Mavrothalassitis, George
AU - Mills, Gordon B.
AU - Domany, Eytan
AU - Yarden, Yosef
PY - 2012/4/1
Y1 - 2012/4/1
N2 - 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.
AB - 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.
KW - Growth factor
KW - Negative feedback
KW - Phosphorylation
KW - Transcription
UR - http://www.scopus.com/inward/record.url?scp=84860899357&partnerID=8YFLogxK
U2 - 10.1096/fj.11-194654
DO - 10.1096/fj.11-194654
M3 - Article
C2 - 22198386
AN - SCOPUS:84860899357
SN - 0892-6638
VL - 26
SP - 1582
EP - 1592
JO - FASEB Journal
JF - FASEB Journal
IS - 4
ER -