EGR1 and the ERK-ERF axis drive mammary cell migration in response to EGF
EGR1 and the ERK-ERF axis drive mammary cell migration in response to EGF
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DOI：
10.1096/fj.11-194654
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发表时间：
2012-04-01
期刊：
影响因子：
4.8
通讯作者：
Yarden, Yosef
中科院分区：
文献类型：
--
作者：
Tarcic, Gabi;Avraham, Roi;Yarden, Yosef
促使细胞迁移的信号通路还不完全清楚。我们使用了人类乳腺细胞和两种刺激：诱导细胞迁移的表皮生长因子(EGF)和刺激细胞生长的血清因子。除了EGF和AKT对ERK的强烈激活外，早期转录也有显著的不同：EGF诱导早期生长反应-1(Egr1)，这是迁移所必需的，血清诱导c-Fos和FosB促进增殖。我们证明了Egr1的诱导涉及ERK介导的microRNA-191的下调和ETS2抑制因子(ERF)的磷酸化，后者随后离开细胞核。出乎意料的是，ERF的敲除抑制了迁移，这意味着输出的ERF分子具有迁移作用。另一方面，染色质免疫沉淀鉴定了一组直接的Egr1靶点，包括Egr1自我刺激和SERPINB2，它们的转录对于EGF诱导的细胞迁移是必不可少的。总之，Egr1和EGF-ERK-ERF轴是生长因子诱导的乳腺细胞迁移的主要驱动因素。-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.Egr1和ERK-ERF轴驱动乳腺细胞对EGF的迁移。FASE B J.26,1582-1592(2012)。Www.fasebj.org
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.-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. EGR1 and the ERK-ERF axis drive mammary cell migration in response to EGF. FASEB J. 26, 1582-1592 (2012). www.fasebj.org