Zyxin Mediates Actin Fiber Reorganization in Epithelial-Mesenchymal Transition and Contributes to Endocardial Morphogenesis
Zyxin Mediates Actin Fiber Reorganization in Epithelial-Mesenchymal Transition and Contributes to Endocardial Morphogenesis
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DOI：
10.1091/mbc.e09-01-0046
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发表时间：
2009-07-01
影响因子：
3.3
通讯作者：
Kaneda, Yasufumi
中科院分区：
文献类型：
--
作者：
Mori, Masaki;Nakagami, Hironori;Kaneda, Yasufumi
上皮-间质转化（EMT）使形态发生或癌症转移所需的细胞-细胞粘附和细胞运动不稳定。在这里，我们报告zyxin，一个局灶性粘附相关的LIM蛋白，是必不可少的肌动蛋白重组的细胞迁移在TGF-β 1诱导的EMT在正常小鼠乳腺（NMuMG）细胞。TGF-β 1诱导zyxin从粘着斑迁移到肌动蛋白纤维。此外，TGF-β 1通过转录因子Twist 1上调zyxin。zyxin或Twist 1的缺失消除了TGF-β 1依赖的EMT，包括增强的细胞运动性和肌动蛋白重组，表明TGF-β 1-Twist 1-zyxin信号用于EMT。zyxin和Twist 1都主要在心脏发育过程中经历EMT的心脏房室管（AVC）中表达。我们进一步进行了离体AVC外植体试验，发现zyxin是肌动蛋白纤维重组和内皮细胞迁移所必需的。因此，zyxin重组肌动蛋白纤维并增强细胞对TGF-β 1的运动性，从而调节EMT。
Epithelial-mesenchymal transition (EMT) confers destabilization of cell-cell adhesion and cell motility required for morphogenesis or cancer metastasis. Here we report that zyxin, a focal adhesion-associated LIM protein, is essential for actin reorganization for cell migration in TGF-beta 1-induced EMT in normal murine mammary gland (NMuMG) cells. TGF-beta 1 induced the relocation of zyxin from focal adhesions to actin fibers. In addition, TGF-beta 1 up-regulated zyxin via a transcription factor, Twist1. Depletion of either zyxin or Twist1 abrogated the TGF-beta 1-dependent EMT, including enhanced cell motility and actin reorganization, indicating the TGF-beta 1-Twist1-zyxin signal for EMT. Both zyxin and Twist1 were predominantly expressed in the cardiac atrioventricular canal (AVC) that undergoes EMT during heart development. We further performed ex vivo AVC explant assay and revealed that zyxin was required for the reorganization of actin fibers and migration of the endocardial cells. Thus, zyxin reorganizes actin fibers and enhances cell motility in response to TGF-beta 1, thereby regulating EMT.