N-cadherin dependent collective cell invasion of prostate cancer cells is regulated by the N-terminus of α-catenin.
N-cadherin dependent collective cell invasion of prostate cancer cells is regulated by the N-terminus of α-catenin.
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DOI：
10.1371/journal.pone.0055069
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Yamada S
中科院分区：
文献类型：
--
作者：
Cui Y;Yamada S
癌细胞侵袭是转移的关键第一步，然而，关于癌细胞如何在复杂的细胞外基质中侵袭并启动转移的知之甚少。使用来自前列腺癌骨转移（PC 3）的细胞系，我们分析了前列腺癌细胞如何在生理相关的3D Matrigel中迁移。我们发现，PC 3细胞迁移更有效地作为多细胞簇比孤立的单细胞，这表明细胞-细胞粘附的存在改善了三维细胞迁移。通过转染N-钙粘蛋白胞质结构域或N-钙粘蛋白特异性shRNA来干扰N-钙粘蛋白功能，可消除集体细胞迁移。有趣的是，PC 3细胞不表达α-catenin，一种钙粘蛋白复合物中的肌动蛋白结合蛋白。当重新引入全长α-连环蛋白时，PC 3细胞的表型恢复到更上皮化的表型，并且在3D Matrigel中细胞迁移率降低。有趣的是，我们发现α-连环蛋白的N末端一半足以抑制侵袭性表型。总之，这些数据表明，N-钙粘蛋白连接的形成促进前列腺癌细胞的3D细胞迁移，这部分是由于在α-连环蛋白缺乏的情况下，N-钙粘蛋白复合物的异常调节。
Cancer cell invasion is the critical first step of metastasis, yet, little is known about how cancer cells invade and initiate metastasis in a complex extracellular matrix. Using a cell line from bone metastasis of prostate cancer (PC3), we analyzed how prostate cancer cells migrate in a physiologically relevant 3D Matrigel. We found that PC3 cells migrated more efficiently as multi-cellular clusters than isolated single cells, suggesting that the presence of cell-cell adhesion improves 3D cell migration. Perturbation of N-cadherin function by transfection of either the N-cadherin cytoplasmic domain or shRNA specific to N-cadherin abolished collective cell migration. Interestingly, PC3 cells do not express α-catenin, an actin binding protein in the cadherin complex. When the full-length α-catenin was re-introduced, the phenotype of PC3 cells reverted back to a more epithelial phenotype with a decreased cell migration rate in 3D Matrigel. Interestingly, we found that the N-terminal half of α-catenin was sufficient to suppress invasive phenotype. Taken together, these data suggest that the formation of N-cadherin junctions promotes 3D cell migration of prostate cancer cells, and this is partly due to an aberrant regulation of the N-cadherin complex in the absence of α-catenin.
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影响因子：
64.5
作者：
Drees, F;Pokutta, S;Weis, WI
通讯作者：
Weis, WI
N-钙粘着蛋白在乳腺癌细胞中的外源表达会诱导细胞迁移，侵袭和转移。
影响因子：
7.8
作者：
Hazan, R B;Phillips, G R;Qiao, R F;Norton, L;Aaronson, S A
通讯作者：
Aaronson, S A
DOI：
10.1083/jcb.201001149
发表时间：
2010-06-28
期刊：
The Journal of cell biology
影响因子：
--
作者：
le Duc Q;Shi Q;Blonk I;Sonnenberg A;Wang N;Leckband D;de Rooij J
通讯作者：
de Rooij J
影响因子：
8.8
作者：
Morita, N;Uemura, H;Tsumatani, K;Cho, M;Hirao, Y;Okajima, E;Konishi, N;Hiasa, Y
通讯作者：
Hiasa, Y
影响因子：
6.4
作者：
Patel, IS;Madan, P;MacCalman, CD
通讯作者：
MacCalman, CD