MicroRNA-584 and the Protein Phosphatase and Actin Regulator 1 (PHACTR1), a New Signaling Route through Which Transforming Growth Factor-β Mediates the Migration and Actin Dynamics of Breast Cancer Cells
MicroRNA-584 and the Protein Phosphatase and Actin Regulator 1 (PHACTR1), a New Signaling Route through Which Transforming Growth Factor-β Mediates the Migration and Actin Dynamics of Breast Cancer Cells
复制标题
DOI：
10.1074/jbc.m112.430934
复制
发表时间：
2013-04-26
影响因子：
4.8
通讯作者：
Lebrun, Jean-Jacques
中科院分区：
文献类型：
--
作者：
Fils-Aime, Nadege;Dai, Meiou;Lebrun, Jean-Jacques
tgf - β作为一种前转移因子在乳腺癌进展中发挥重要作用，特别是通过增强细胞迁移。越来越清楚的是，microrna作为一类新的小调控分子，在介导肿瘤的形成和进展中也起着至关重要的作用。我们发现tgf - β下调乳腺癌细胞中microRNA miR-584的表达。此外，我们发现PHACTR1（一种肌动蛋白结合蛋白）以miR584依赖的方式受到tgf - β的正向调节。此外，我们发现tgf - β介导的miR-584下调和PHACTR1表达增加是tgf - β诱导的乳腺癌细胞迁移所必需的。事实上，miR-584的过表达和PHACTR1的敲低都会导致肌动蛋白细胞骨架的剧烈重组，并减少tgf - β诱导的细胞迁移。我们的数据强调了一种新的信号通路，即tgf - β沉默miR-584的表达，导致PHACTR1表达增强，并进一步导致肌动蛋白重排和乳腺癌细胞迁移。
TGF-beta plays an important role in breast cancer progression as a prometastatic factor, notably through enhancement of cell migration. It is becoming clear that microRNAs, a new class of small regulatory molecules, also play crucial roles in mediating tumor formation and progression. We found TGF-beta to downregulate the expression of the microRNA miR-584 in breast cancer cells. Furthermore, we identified PHACTR1, an actin-binding protein, to be positively regulated by TGF-beta in a miR584- dependent manner. Moreover, we found TGF-beta-mediated down-regulation of miR-584 and increased expression of PHACTR1 to be required for TGF-beta-induced cell migration of breast cancer cells. Indeed, both overexpression of miR-584 and knockdown of PHACTR1 resulted in a drastic reorganization of the actin cytoskeleton and reduced TGF-beta-induced cell migration. Our data highlight a novel signaling route whereby TGF-beta silences the expression of miR-584, resulting in enhanced PHACTR1 expression, and further leading to actin rearrangement and breast cancer cell migration.