Directional cell movement through tissues is controlled by exosome secretion.
Directional cell movement through tissues is controlled by exosome secretion.
复制标题
DOI：
10.1038/ncomms8164
复制
发表时间：
2015-05-13
影响因子：
16.6
通讯作者：
Weaver, Alissa M.
中科院分区：
文献类型：
--
作者：
Sung, Bong Hwan;Ketova, Tatiana;Hoshino, Daisuke;Zijlstra, Andries;Weaver, Alissa M.
细胞在组织中的定向运动对于多种生物过程至关重要，并且在面对复杂的环境线索时需要维持极性。在这里，我们使用活体成像来证明晚期内体分泌外泌体是癌细胞定向持久和有效体内运动所需的。抑制外泌体分泌或生物发生导致与不稳定突起的形成增加和过度方向转换相关的缺陷性肿瘤细胞迁移。用纯化的外泌体和基质涂层进行的体外拯救实验将粘附组装鉴定为促进有效细胞运动的关键外泌体功能。活细胞成像显示，外泌体分泌直接先于并促进粘附组装。纤连蛋白被发现是一种关键的促进运动的货物，其分选到外泌体取决于结合到整合素。我们认为，外泌体的自分泌通过加强短暂的极化状态和促进粘附组装，有力地促进定向持久和有效的细胞运动。 细胞在复杂环境中迁移时如何保持方向极性还不清楚。在此，Sung等人表明，自分泌外泌体分泌是持续和有效的体内癌细胞运动所需的，并通过递送纤连蛋白结合的外泌体促进粘附复合物的组装。
Directional cell movement through tissues is critical for multiple biological processes and requires maintenance of polarity in the face of complex environmental cues. Here we use intravital imaging to demonstrate that secretion of exosomes from late endosomes is required for directionally persistent and efficient in vivo movement of cancer cells. Inhibiting exosome secretion or biogenesis leads to defective tumour cell migration associated with increased formation of unstable protrusions and excessive directional switching. In vitro rescue experiments with purified exosomes and matrix coating identify adhesion assembly as a critical exosome function that promotes efficient cell motility. Live-cell imaging reveals that exosome secretion directly precedes and promotes adhesion assembly. Fibronectin is found to be a critical motility-promoting cargo whose sorting into exosomes depends on binding to integrins. We propose that autocrine secretion of exosomes powerfully promotes directionally persistent and effective cell motility by reinforcing otherwise transient polarization states and promoting adhesion assembly. How cells maintain directional polarity when migrating through a complex environment is not well understood. Here Sung et al. show that autocrine exosome secretion is required for persistent and efficient in vivo cancer cell motility and promotes assembly of adhesion complexes by delivering fibronectin-bound exosomes.
登录
查看更多内容
影响因子：
30.5
作者：
通讯作者：
--
影响因子：
--
作者：
Berginski ME;Gomez SM
通讯作者：
Gomez SM
影响因子：
3.7
作者：
Borm, B;Requardt, RP;Kirfel, G
通讯作者：
Kirfel, G
影响因子：
11.8
作者：
Lobert, Viola Helene;Brech, Andreas;Stenmark, Harald
通讯作者：
Stenmark, Harald
影响因子：
7.5
作者：
Margadant, Coert;Monsuur, Hanneke N.;Sonnenberg, Arnoud
通讯作者：
Sonnenberg, Arnoud