Mesenchymal cells reactivate Snail1 expression to drive three-dimensional invasion programs.
Mesenchymal cells reactivate Snail1 expression to drive three-dimensional invasion programs.
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DOI：
10.1083/jcb.200810113
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发表时间：
2009-02-09
影响因子：
7.8
通讯作者：
Weiss, Stephen J.
中科院分区：
文献类型：
--
作者：
Rowe, R. Grant;Li, Xiao-Yan;Hu, Yuexian;Saunders, Thomas L.;Virtanen, Ismo;de Herreros, Antonio Garcia;Becker, Karl-Friedrich;Ingvarsen, Signe;Engelholm, Lars H.;Bommer, Guido T.;Fearon, Eric R.;Weiss, Stephen J.
上皮-间充质转化（EMT）是发育过程中胚层分化所必需的。锌指转录因子Snail 1可以触发EMT，并足以在肿瘤形成和纤维化过程中将上皮细胞转录重编程为间充质表型。Snail 1是否也调节终末分化的间充质细胞的行为仍有待研究。使用Snai 1条件性敲除模型，我们现在确定Snai 1作为正常间充质细胞功能的调节因子。Snail 1在正常成纤维细胞中的表达可由已知促进体内增殖和侵袭的激动剂诱导。当在组织样三维细胞外基质中受到挑战时，Snail 1缺陷型成纤维细胞表现出基因表达的全局变化，其中包括膜1型基质金属蛋白酶（MT 1-MMP）依赖性侵袭活性的缺陷。活鸡胚绒毛尿囊膜上的Snail 1缺陷型成纤维细胞缺乏组织侵袭能力，不能诱导血管生成。这些发现确立了间充质细胞终末分化后EMT调节因子Snail 1的关键功能。
Epithelial–mesenchymal transition (EMT) is required for mesodermal differentiation during development. The zinc-finger transcription factor, Snail1, can trigger EMT and is sufficient to transcriptionally reprogram epithelial cells toward a mesenchymal phenotype during neoplasia and fibrosis. Whether Snail1 also regulates the behavior of terminally differentiated mesenchymal cells remains unexplored. Using a Snai1 conditional knockout model, we now identify Snail1 as a regulator of normal mesenchymal cell function. Snail1 expression in normal fibroblasts can be induced by agonists known to promote proliferation and invasion in vivo. When challenged within a tissue-like, three-dimensional extracellular matrix, Snail1-deficient fibroblasts exhibit global alterations in gene expression, which include defects in membrane type-1 matrix metalloproteinase (MT1-MMP)-dependent invasive activity. Snail1-deficient fibroblasts explanted atop the live chick chorioallantoic membrane lack tissue-invasive potential and fail to induce angiogenesis. These findings establish key functions for the EMT regulator Snail1 after terminal differentiation of mesenchymal cells.
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