Membrane-type 1 matrix metalloproteinase regulates cell migration during zebrafish gastrulation: Evidence for an interaction with non-canonical Wnt signaling
Membrane-type 1 matrix metalloproteinase regulates cell migration during zebrafish gastrulation: Evidence for an interaction with non-canonical Wnt signaling
复制标题
DOI：
10.1016/j.yexcr.2008.03.010
复制
发表时间：
2008-06-10
影响因子：
3.7
通讯作者：
Jessen, Jason R.
中科院分区：
文献类型：
--
作者：
Coyle, Rebecca C.;Latimer, Andrew;Jessen, Jason R.
侵袭性的关键是肿瘤细胞能够改变细胞外基质，变得能动，并参与向脉管系统的定向迁移。与转移进展相关的一种重要蛋白质是膜型1基质金属蛋白酶（MT 1-MMP/MMP 14）。MMP 14活性如何与其他信号通路协调以调节体内细胞迁移在很大程度上是未知的。在这里，我们使用斑马鱼胚胎发生作为模型，以了解MMP 14依赖的细胞周围蛋白水解，细胞极性和运动之间的潜在关系。斑马鱼Mmp 14功能的敲除破坏了原肠胚的会聚和延伸，细胞运动和颅面形态发生。使用延时成像和形态学分析，我们表明，Mmp 14是必需的适当的细胞极性的基础上的中胚层细胞在原肠胚形成的定向迁移。我们已经确定了mmp 14和非经典Writ信号之间的遗传相互作用，这是一种也调节胚胎组织中细胞极性的途径，并且越来越多地与肿瘤细胞迁移有关。最后，我们证明，货车高赫样2，非经典的Writ通路的关键调节器，共定位与MMP 14，并成为重新分配向极化的人类癌细胞的前沿。总之，我们的研究结果支持的概念，调节细胞周围蛋白水解和细胞极性的途径收敛，以促进有效的细胞迁移。(c)2008年爱思唯尔公司All rights reserved.
Key to invasiveness is the ability of tumor cells to modify the extracellular matrix, become motile, and engage in directed migration towards the vasculature. One significant protein associated with metastatic progression is membrane-type 1 matrix metalloproteinase (MT1-MMP/MMP14). How MMP14 activity is coordinated with other signaling pathways to regulate cell migration in vivo is largely unknown. Here we have used zebrafish embryogenesis as a model to understand the potential relationship between MMP14-dependent pericellular proteolysis, cell polarity, and motility. Knockdown of zebrafish Mmp14 function disrupted gastrulation convergence and extension cell movements and craniofacial morphogenesis. Using time-lapse imaging and morphometric analyses, we show that Mmp14 is required for proper cell polarity underlying the directed migration of mesodermal cells during gastrulation. We have identified a genetic interaction between mmp14 and non-canonical Writ signaling, a pathway that also regulates cell polarity in embryonic tissues and is increasingly being linked with tumor cell migration. Finally, we demonstrate that Van Gogh-like 2, a key regulator of the non-canonical Writ pathway, co-localizes with MMP14 and becomes redistributed towards the leading edge of polarized human cancer cells. Together, our results support the notion that pathways regulating pericellular proteolysis and cell polarity converge to promote efficient cell migration. (c) 2008 Elsevier Inc. All rights reserved.