Vimentin intermediate filament and plectin provide a scaffold for invadopodia, facilitating cancer cell invasion and extravasation for metastasis.
Vimentin intermediate filament and plectin provide a scaffold for invadopodia, facilitating cancer cell invasion and extravasation for metastasis.
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DOI：
10.1016/j.ejcb.2014.03.002
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发表时间：
2014-04
影响因子：
6.6
通讯作者：
M. Sutoh Yoneyama;S. Hatakeyama;T. Habuchi;T. Inoue;Toshiya Nakamura;T. Funyu;G. Wiche;C. Ohyama;S. Tsuboi
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文献类型：
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作者：
M. Sutoh Yoneyama;S. Hatakeyama;T. Habuchi;T. Inoue;Toshiya Nakamura;T. Funyu;G. Wiche;C. Ohyama;S. Tsuboi
为了研究膀胱癌转移的分子机制，我们利用anin活体选择系统从低转移细胞系中分离出一个高转移膀胱癌细胞亚群。该亚群中的细胞表现出形成侵足的高能力，即丝状肌动蛋白（F-actin）为基础的膜突起，在癌细胞侵袭中起重要作用。基因表达谱分析显示，与低转移细胞系相比，高转移亚群中中间丝蛋白（IF） vimentin和细胞骨架连接蛋白plectin表达上调。在这里，我们报告了一个新的作用，波形蛋白，IF和凝集素在转移。在侵袭性膀胱癌细胞中，形成了vimentin - if -plectin- invadopdia F-actin连接。这种联系的破坏严重损害了内殖泡的形成，降低了细胞外基质降解、跨内皮迁移和转移的能力。此外，进入细丝的弧菌蛋白组装是侵殖体形成所必需的。我们的研究结果表明，粘附素将浸润样细胞锚定在波形蛋白IF支架上并稳定浸润样细胞，这是癌细胞侵袭和外渗转移的关键分子过程。
To investigate the molecular mechanisms of cancer metastasis, we have isolated a high-metastatic bladder cancer cell subpopulation from a low-metastatic cell line by using anin vivoselection system. Cells in the subpopulation showed a high ability to form invadopodia, the filamentous actin (F-actin)-based membrane protrusions that play an essential role in cancer cell invasion. Analysis of the gene expression profile revealed that the expression of an intermediate filament (IF) protein, vimentin and a cytoskeletal linker protein, plectin was up-regulated in the high-metastatic subpopulation compared with the low metastatic cell line. Here we report a novel role of vimentin IF and plectin in metastasis. In invasive bladder cancer cells, the vimentin IF-plectin-invadopodia F-actin link was formed. Disruption of this link severely impaired invadopodia formation, reducing the capacities of extracellular matrix degradation, transendothelial migration and metastasis. In addition, the vimentin assembly into the filaments was required for invadopodia formation. Our results suggest that plectin anchoring invadopodia to vimentin IF scaffolds and stabilizes invadopodia, which is a critical molecular process for cancer cell invasion and extravasation for metastasis.