Cell invasion through basement membrane: The netrin receptor DCC guides the way.
Cell invasion through basement membrane: The netrin receptor DCC guides the way.
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DOI：
10.4161/worm.26169
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发表时间：
2013-07-01
期刊：
影响因子：
--
通讯作者：
Sherwood DR
中科院分区：
文献类型：
--
作者：
Morrissey MA;Hagedorn EJ;Sherwood DR
细胞通过基底膜侵入是正常发育和生理的重要组成部分，并且发生在人类炎症性疾病和癌症的病理进展期间。富含F-肌动蛋白的膜突起，称为侵袭伪足，被假设为侵袭细胞的“钻头”，介导通过致密的、高度交联的基底膜基质的侵袭。虽然在体外研究了30多年，但侵入伪足在体内的功能仍然难以捉摸。我们最近发现，在C.锚细胞入侵过程中，入侵伪足突破基底膜。线虫，一种遗传上和视觉上易于处理的体内入侵事件。此外，我们发现netrin受体DCC定位于基底膜破裂的初始位点，并通过基质中的单个间隙引导侵袭。在这篇评论中，我们研究了AC-侵袭伪足的动力学和结构与体外侵袭伪足的比较，以及netrin受体如何通过单个基底膜破裂来引导侵袭。最后，我们讨论了我们令人惊讶的结果，即锚细胞将基底膜推到一边，而不是通过蛋白水解完全溶解基底膜，并为蛋白酶和物理置换如何协同工作以确保有效和强大的入侵提供了一些想法。
Cell invasion through basement membrane is an essential part of normal development and physiology, and occurs during the pathological progression of human inflammatory diseases and cancer. F-actin-rich membrane protrusions, called invadopodia, have been hypothesized to be the “drill bits” of invasive cells, mediating invasion through the dense, highly cross-linked basement membrane matrix. Though studied in vitro for over 30 y, invadopodia function in vivo has remained elusive. We have recently discovered that invadopodia breach basement membrane during anchor cell invasion in C. elegans, a genetically and visually tractable in vivo invasion event. Further, we found that the netrin receptor DCC localizes to the initial site of basement membrane breach and directs invasion through a single gap in the matrix. In this commentary, we examine how the dynamics and structure of AC-invadopodia compare with in vitro invadopodia and how the netrin receptor guides invasion through a single basement membrane breach. We end with a discussion of our surprising result that the anchor cell pushes the basement membrane aside, instead of completely dissolving it through proteolysis, and provide some ideas for how proteases and physical displacement may work together to ensure efficient and robust invasion.