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首页> 外文期刊>Cellular Signalling >Wnt6 induces the specification and epithelialization of F9 embryonal. carcinoma cells to primitive endoderm
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Wnt6 induces the specification and epithelialization of F9 embryonal. carcinoma cells to primitive endoderm

机译：Wnt6诱导F9胚胎的规格和上皮形成。癌细胞到原始内胚层

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Epithelial-to-mesenchymal transitions (EMTs) play key roles in the normal development of an organism as well as its demise following the metastasis of a malignant tumour. An EMT during early mouse development results in the differentiation of primitive endoderm into the parietal endoderm that forms part of the parietal yolk sac. In the embryo, primitive endoderm develops from cells in the inner cell mass, but the signals that instruct these cells to become specified and adopt an epithelial fate are poorly understood. The mouse F9 teratocarcinoma cell line, a model that can recapitulate the in vivo primitive to parietal endoderm EMT, has been used extensively to elucidate the signalling cascades involved in extraembryonic endoderm differentiation. Here, we identified Wnt6 as a gene up-regulated in F9 cells in response to RA and show that Wnt6 expressing cells or cells exposed to Wnt6 conditioned media form primitive endoderm. Wnt6 induction of primitive endoderm is accompanied by p-catenin and Snail1 translocation to the nucleus and the appearance of cytokeratin intermediate filaments. Attenuating glycogen synthase kinase 3 activity using LiCl gave similar results, but the fact that cells de-differentiate when LiCl is removed reveals that other signalling pathways are required to maintain cells as primitive endoderm. Finally, Wnt6-induced primitive endodermal cells were tested to determine their competency to complete the EMT and differentiate into parietal endoderm. Towards that end, results show that up-regulating protein kinase A activity is sufficient to induce markers of parietal endoderm. Together, these findings indicate that undifferentiated F9 cells are responsive to canonical Wnt signalling, which negatively regulates glycogen synthase kinase 3 activity leading to the epithelialization and specification of primitive endoderm competent to, receive additional signals required for EMT. Considering the ability of F9 cells to mimic an in vivo EMT, the identification of this Wnt6-beta-catenin-Snail signalling cascade has broad implications for understanding EMT mechanisms in embryogenesis and metastasis. (C) 2007 Elsevier Inc. All rights reserved.
机译：上皮-间质转化（EMT）在生物体正常发育以及恶性肿瘤转移后的死亡中起着关键作用。小鼠早期发育过程中的EMT导致原始内胚层分化为形成壁卵黄囊一部分的壁内胚层。在胚胎中，原始内胚层是从内部细胞团中的细胞发育而来的，但是对指示这些细胞变得特定并采用上皮命运的信号知之甚少。小鼠F9畸胎瘤细胞系是一种可以将体内原始基因还原为顶内胚层EMT的模型，已广泛用于阐明涉及胚外内胚层分化的信号级联反应。在这里，我们将Wnt6鉴定为对RA响应的F9细胞中上调的基因，并显示Wnt6表达细胞或暴露于Wnt6条件培养基的细胞形成原始内胚层。 Wnt6诱导的原始内胚层伴随有p-catenin和Snail1易位至细胞核以及细胞角蛋白中间丝的出现。使用LiCl减弱糖原合酶激酶3的活性也得到了相似的结果，但是当LiCl被去除时细胞去分化的事实表明，还需要其他信号通路来维持细胞为原始内胚层。最后，测试了Wnt6诱导的原始内胚层细胞，以确定其完成EMT并分化为顶内胚层的能力。为此，结果表明，上调蛋白激酶A的活性足以诱导壁突内胚层的标志物。在一起，这些发现表明未分化的F9细胞对规范的Wnt信号作出反应，从而负向调节糖原合酶激酶3的活性，从而导致原始内胚层的上皮形成和规范能够接收EMT所需的其他信号。考虑到F9细胞模拟体内EMT的能力，此Wnt6-β-catenin-Snail信号级联的鉴定对于理解EMT在胚胎发生和转移中的机制具有广泛的意义。 （C）2007 Elsevier Inc.保留所有权利。

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