EGR1 and the ERK-ERF axis drive mammary cell migration in response to EGF

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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    57 Scopus citations

    Abstract

    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.

    Original languageEnglish (US)
    Pages (from-to)1582-1592
    Number of pages11
    JournalFASEB Journal
    Volume26
    Issue number4
    DOIs
    StatePublished - Apr 1 2012

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    Keywords

    • Growth factor
    • Negative feedback
    • Phosphorylation
    • Transcription

    ASJC Scopus subject areas

    • Biotechnology
    • Biochemistry
    • Molecular Biology
    • Genetics

    Cite this

    Tarcic, G., Avraham, R., Pines, G., Amit, I., Shay, T., Lu, Y., Zwang, Y., Katz, M., Ben-Chetrit, N., Jacob-Hirsch, J., Virgilio, L., Rechavi, G., Mavrothalassitis, G., Mills, G. B., Domany, E., & Yarden, Y. (2012). EGR1 and the ERK-ERF axis drive mammary cell migration in response to EGF. FASEB Journal, 26(4), 1582-1592. https://doi.org/10.1096/fj.11-194654