Paracrine regulation of neural crest EMT by placodal MMP28.

IF 7.8 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY PLoS Biology Pub Date : 2023-08-17 eCollection Date: 2023-08-01 DOI:10.1371/journal.pbio.3002261
Nadège Gouignard, Anne Bibonne, João F Mata, Fernanda Bajanca, Bianka Berki, Elias H Barriga, Jean-Pierre Saint-Jeannet, Eric Theveneau
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Abstract

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.

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MMP28对神经嵴EMT的旁分泌调节。
上皮-间充质转化(EMT)是上皮组织细胞扩散的早期事件。EMT赋予细胞迁移,有时是侵袭的能力,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)中的基质重塑作用。在这里,我们使用非洲爪蟾神经嵴细胞来评估MMP28在EMT和体内迁移中的作用。我们发现,由邻近的板尾细胞表达的具有催化活性的MMP28是神经嵴EMT和细胞迁移所必需的。我们提供了强有力的证据,表明MMP28是在神经嵴细胞的细胞核中输入的,在那里它是正常Twist表达所必需的。我们的数据表明,MMP28可以在体内作为EMT的上游调节因子,这增加了其他MMP在各种EMT相关背景下(如癌症、纤维化和伤口愈合)可能具有类似早期作用的可能性。
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来源期刊
PLoS Biology
PLoS Biology 生物-生化与分子生物学
CiteScore
14.40
自引率
2.00%
发文量
359
审稿时长
3 months
期刊介绍: PLOS Biology is an open-access, peer-reviewed general biology journal published by PLOS, a nonprofit organization of scientists and physicians dedicated to making the world's scientific and medical literature freely accessible. The journal publishes new articles online weekly, with issues compiled and published monthly. ISSN Numbers: eISSN: 1545-7885 ISSN: 1544-9173
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