Paracrine regulation of neural crest EMT by placodal MMP28.
Paracrine regulation of neural crest EMT by placodal MMP28.
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DOI：
10.1371/journal.pbio.3002261
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发表时间：
2023-08
期刊：
影响因子：
9.8
通讯作者：
中科院分区：
文献类型：
--
作者：
上皮-间质转化（EMT）是上皮组织细胞播散的早期事件。EMT赋予细胞迁移，有时是侵入性的能力，因此是胚胎形态发生和癌症进展的关键过程。到目前为止，基质金属蛋白酶（MMPs）还没有被认为是EMT中的关键参与者，而是研究了它们在后期事件（如细胞迁移本身）中基质重塑的作用。在这里，我们使用非洲爪蟾神经嵴细胞来评估MMP 28在体内EMT和迁移中的作用。我们发现，一个催化活性MMP 28，相邻基板细胞表达，是需要神经嵴EMT和细胞迁移。我们提供了强有力的证据表明，MMP 28是进口的神经嵴细胞的细胞核中，它是需要正常的扭曲表达。我们的数据表明，MMP 28可以作为体内EMT的上游调节因子，这提高了其他MMPs在各种EMT相关环境（如癌症、纤维化和伤口愈合）中可能具有类似早期作用的可能性。上皮-间质转化（EMT）是上皮组织细胞播散的早期事件。这项对两栖动物非洲爪蟾胚胎的研究表明，金属蛋白酶MMP 28由基板产生，并在邻近神经嵴细胞的核内起作用，以触发EMT。
Epithelial–mesenchymal transition (EMT) is an early event in cell dissemination from epithelial tissues. EMT endows cells with migratory, and sometimes invasive, capabilities and is thus a key process in embryo morphogenesis and cancer progression. So far, matrix metalloproteinases (MMPs) have not been considered as key players in EMT but rather studied for their role in matrix remodelling in later events such as cell migration per se. Here, we used Xenopus neural crest cells to assess the role of MMP28 in EMT and migration in vivo. We show that a catalytically active MMP28, expressed by neighbouring placodal cells, is required for neural crest EMT and cell migration. We provide strong evidence indicating that MMP28 is imported in the nucleus of neural crest cells where it is required for normal Twist expression. Our data demonstrate that MMP28 can act as an upstream regulator of EMT in vivo raising the possibility that other MMPs might have similar early roles in various EMT-related contexts such as cancer, fibrosis, and wound healing. Epithelial-mesenchymal transition (EMT) is an early event in cell dissemination from epithelial tissues. This study in embryos of the amphibian Xenopus laevis reveals that the metalloproteinase MMP28 is produced by placodes and acts inside the nucleus of neighboring neural crest cells to trigger EMT.
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