Centre de Biologie du Développement, Centre de Biologie Intégrative, Université de Toulouse, CNRS, UPS, Toulouse, 31062, France.
Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, MA 01003, USA.
Development. 2020 Apr 12;147(7):dev183954. doi: 10.1242/dev.183954.
Matrix metalloproteinases have a broad spectrum of substrates ranging from extracellular matrix components and adhesion molecules to chemokines and growth factors. Despite being mostly secreted, MMPs have been detected in the cytosol, the mitochondria or the nucleus. Although most of the attention is focused on their role in matrix remodeling, the diversity of their substrates and their complex trafficking open the possibility for non-canonical functions. Yet examples and experimental demonstration of the physiological relevance of such activities are rare. Here, we have used chick neural crest (NC) cells, a highly migratory stem cell population likened to invasive cancer cells, as a model for physiological epithelial-mesenchymal transition (EMT). We demonstrate that MMP14 is required for NC delamination. Interestingly, this role is independent of its cytoplasmic tail and of its catalytic activity. Our data indicate that, in addition to being a late pro-invasive factor, MMP14 is also likely to be an early player, owing to its role in EMT.
基质金属蛋白酶（MMPs）具有广泛的底物谱，包括细胞外基质成分和黏附分子、趋化因子和生长因子。尽管 MMPs 主要被分泌，但也在细胞质、线粒体或核内检测到。尽管大多数注意力集中在它们在基质重塑中的作用，但它们的底物的多样性和它们的复杂运输为非典型功能开辟了可能性。然而，这种活性的生理相关性的例子和实验证明很少。在这里，我们使用鸡神经嵴（NC）细胞作为生理上皮-间充质转化（EMT）的模型，这是一种类似于侵袭性癌细胞的高度迁移的干细胞群体。我们证明 MMP14 对于 NC 的分层是必需的。有趣的是，这个作用不依赖于其细胞质尾巴和催化活性。我们的数据表明，MMP14 不仅是晚期的促侵袭因子，而且由于其在 EMT 中的作用，它也可能是早期的参与者。
