Filopodia and adhesion in cancer cell motility
Filopodia and adhesion in cancer cell motility
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DOI：
10.4161/cam.5.5.17723
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发表时间：
2011-09-01
影响因子：
3.2
通讯作者：
Ivaska, Johanna
中科院分区：
文献类型：
--
作者：
Arjonen, Antti;Kaukonen, Riina;Ivaska, Johanna
含有质膜突起的细长束状肌动蛋白，被称为丝状伪足，对许多基本的细胞过程非常重要，例如细胞黏附、迁移、血管生成以及细胞 - 细胞接触的形成。在迁移的细胞中，丝状伪足是前沿的先锋，它们探测环境以获取线索。整合素是细胞表面黏附受体，在细胞迁移中起着关键作用，它们通过一种非常规的肌球蛋白——肌球蛋白 - X被主动运输到丝状伪足的尖端。整合素介导的黏附稳定丝状伪足并促进细胞迁移，尽管整合素对丝状伪足的起始不是必需的。肌球蛋白 - X还与磷脂酰肌醇 - 3,4,5 - 三磷酸（PtdIns(3,4,5)P - 3）结合，这调节其活化以及在丝状伪足中的定位。丝状伪足在许多细胞类型中刺激细胞迁移，并且在癌症中已发现丝状伪足密度增加。此外，一些与丝状伪足形成有关的蛋白质，如肌动蛋白集束蛋白（fascin），也与癌症进展相关。为了进一步研究这一点，我们对人类乳腺癌中10个与丝状伪足相关的基因的表达谱进行了荟萃分析。这些数据表明，几个不同的丝状伪足诱导基因可能以一种共同的方式促进癌症进展以及与基底型乳腺癌相关的高转移率。
Slender bundled actin containing plasma membrane protrusions, called filopodia, are important for many essential cellular processes like cell adhesion, migration, angiogenesis and the formation of cell-cell contacts. In migrating cells, filopodia are the pioneers at the leading edge which probe the environment for cues. Integrins are cell surface adhesion receptors critically implicated in cell migration and they are transported actively to filopodia tips by an unconventional myosin, myosin-X. Integrin mediated adhesion stabilizes filopodia and promotes cell migration even though integrins are not essential for filopodia initiation. Myosin-X binds also PtdIns(3,4,5)P-3 and this regulates its activation and localization to filopodia. Filopodia stimulate cell migration in many cell types and increased filopodia density has been described in cancer. Furthermore, several proteins implicated in filopodia formation, like fascin, are also relevant for cancer progression. To investigate this further, we performed a meta-analysis of the expression profiles of 10 filopodia-linked genes in human breast cancer. These data implicated that several different filopodia-inducing genes may contribute in a collective manner to cancer progression and the high metastasis rates associated with basal-type breast carcinomas.