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首页> 外文期刊>Nature >Zinc transporter LIVI controls epithelial-mesenchymal transition in zebrafish gastrula organizer
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Zinc transporter LIVI controls epithelial-mesenchymal transition in zebrafish gastrula organizer

机译：锌转运蛋白LIVI控制斑马鱼胃组织器中的上皮-间质转化

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摘要

Vertebrate gastrulation is a critical step in the establishment of body plan. During gastrulation, epithelial-mesenchymal transition (EMT) occurs(1). EMT is one of the central events of embryonic development, organ and tissue regeneration, and cancer metastasis(1,2). Signal transducers and activators of transcription (STATs) mediate biological actions such as cell proliferation, differentiation and survival in response to cytokines and growth factors, in a variety of biological processes(3-6). STATs are also important in EMT during gastrulation, organogenesis, wound healing and cancer progression(7-9). We previously showed that STAT3 is activated in the organizer during zebrafish gastrulation and its activity is essential for gastrulation movements. The requirement for STAT3 is cell-autonomous for the anterior migration of gastrula organizer cells, and non-cell-autonomous for the convergence of neighbouring cells(10). The molecular mechanisms of STAT's action in EMT, however, are unknown. Here we identify LIV1, a breast-cancer-associated zinc transporter protein(11-13), as a downstream target of STAT3 that is essential and sufficient for STAT3's cell-autonomous role in the EMT of zebrafish gastrula organizer cells. Furthermore, we demonstrate that LIV1 is essential for the nuclear localization of zinc-finger protein Snail, a master regulator of EMT1,2,14,15. These results establish a molecular link between STAT3, LIV1 and Snail in EMT.
机译：脊椎动物气腹是制定人体计划的关键步骤。在胃形成过程中，发生上皮-间质转化（EMT）（1）。 EMT是胚胎发育，器官和组织再生以及癌症转移的重要事件之一（1,2）。信号转导子和转录激活子（STATs）在各种生物过程中介导诸如细胞增殖，分化和存活等对细胞因子和生长因子的生物学作用（3-6）。 STATs在胃动，器官发生，伤口愈合和癌症进展期间对EMT也很重要（7-9）。我们以前的研究表明，STAT3在斑马鱼胃气化过程中在组织器中被激活，其活性对于胃气运动至关重要。 STAT3的要求对于胃脂肪组织细胞的前移是细胞自主的，而对于相邻细胞的融合则不是细胞自主的（10）。 STAT在EMT中起作用的分子机制尚不清楚。在这里，我们确定LIV1，一种与乳腺癌相关的锌转运蛋白（11-13），是STAT3的下游靶标，对于STAT3在斑马鱼腹腔组织细胞EMT中的细胞自主作用而言是必不可少的。此外，我们证明LIV1对于锌指蛋白Snail（EMT1,2,14,15的主要调控因子）的核定位至关重要。这些结果建立了EMT中STAT3，LIV1和Snail之间的分子联系。

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