Schober Markus, Rebay Ilaria, Perrimon Norbert
Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Development. 2005 Aug;132(15):3493-504. doi: 10.1242/dev.01911.
Invasive cell migration in both normal development and metastatic cancer is regulated by various signaling pathways, transcription factors and cell-adhesion molecules. The coordination between these activities in the context of cell migration is poorly understood. During Drosophila oogenesis, a small group of cells called border cells exit the follicular epithelium to perform a stereotypic, invasive migration. We find that the ETS transcription factor Yan is required for border cell migration and that Yan expression is spatiotemporally regulated as border cells migrate from the anterior pole of the egg chamber towards the nurse cell-oocyte boundary. Yan expression is dependent on inputs from the JAK/STAT, Notch and Receptor Tyrosine Kinase pathways in border cells. Mechanistically, Yan functions to modulate the turnover of DE-Cadherin-dependent adhesive complexes to facilitate border cell migration. Our results suggest that Yan acts as a pivotal link between signal transduction, cell adhesion and invasive cell migration in Drosophila border cells.
在正常发育和转移性癌症中,侵袭性细胞迁移受多种信号通路、转录因子和细胞粘附分子调控。在细胞迁移过程中,这些活动之间的协调作用尚不清楚。在果蝇卵子发生过程中,一小群称为边界细胞的细胞离开卵泡上皮,进行刻板的侵袭性迁移。我们发现,ETS转录因子Yan是边界细胞迁移所必需的,并且随着边界细胞从卵室的前极向滋养细胞 - 卵母细胞边界迁移,Yan的表达在时空上受到调控。Yan的表达依赖于边界细胞中JAK/STAT、Notch和受体酪氨酸激酶通路的输入。从机制上讲,Yan通过调节DE - 钙粘蛋白依赖性粘附复合物的周转来促进边界细胞迁移。我们的结果表明,Yan在果蝇边界细胞的信号转导、细胞粘附和侵袭性细胞迁移之间起关键作用。