The RhoGAP protein Deleted in Liver Cancer 3 (DLC3) is essential for adherens junctions integrity.
The RhoGAP protein Deleted in Liver Cancer 3 (DLC3) is essential for adherens junctions integrity.
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DOI：
10.1038/oncsis.2012.13
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发表时间：
2012-06-04
期刊：
影响因子：
6.2
通讯作者：
Olayioye, M. A.
中科院分区：
文献类型：
--
作者：
Holeiter, G.;Bischoff, A.;Braun, A. C.;Huck, B.;Erlmann, P.;Schmid, S.;Herr, R.;Brummer, T.;Olayioye, M. A.
上皮细胞-细胞接触由E-钙粘蛋白相互作用介导，其由Rho GTP酶的平衡局部活性调节。尽管已知的功能，Rho在粘附连接（AJs），很少有人知道的空间控制Rho活性在这些网站。在这里，我们提供的证据表明，在乳腺上皮细胞中，肝癌3（DLC 3）蛋白定位于AJs，是E-钙粘蛋白功能所必需的。DLC 3是一种特征仍然不清楚的RhoA特异性GTP酶激活蛋白，其在各种类型的癌症中经常下调。我们证明DLC 3缺失导致E-钙粘蛋白和连环蛋白的错误定位，这与受损的细胞聚集和增加的迁移有关。这可以通过异常的局部Rho信号传导来解释，因为ROCK抑制恢复了DLC 3敲低细胞中的细胞-细胞接触。因此，我们确定DLC 3作为一种新的负调节连接Rho和建议，DLC 3损失有助于损害上皮完整性的致癌作用。
Epithelial cell–cell contacts are mediated by E-cadherin interactions, which are regulated by the balanced local activity of Rho GTPases. Despite the known function of Rho at adherens junctions (AJs), little is known about the spatial control of Rho activity at these sites. Here we provide evidence that in breast epithelial cells the Deleted in Liver Cancer 3 (DLC3) protein localizes to AJs and is essential for E-cadherin function. DLC3 is a still poorly characterized RhoA-specific GTPase-activating protein that is frequently downregulated in various types of cancer. We demonstrate that DLC3 depletion leads to mislocalization of E-cadherin and catenins, which was associated with impaired cell aggregation and increased migration. This is explained by aberrant local Rho signaling because ROCK inhibition restored cell–cell contacts in DLC3 knockdown cells. We thus identify DLC3 as a novel negative regulator of junctional Rho and propose that DLC3 loss contributes to carcinogenesis by compromising epithelial integrity.
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DLC-1和CTEN的SH2结构域的磷酸酪氨酸独立的相互作用调节局灶性粘附定位和DLC-1的生长抑制活性。
影响因子：
7.8
作者：
Liao, Yi-Chun;Si, Lizhen;White, Ralph W. DeVere;Lo, Su Hao
通讯作者：
Lo, Su Hao
影响因子：
6.6
作者：
Carisey, Alex;Ballestrem, Christoph
通讯作者：
Ballestrem, Christoph
影响因子：
21.3
作者：
Nimnual, AS;Taylor, LJ;Bar-Sagi, D
通讯作者：
Bar-Sagi, D
影响因子：
7.2
作者：
Cavey, Matthieu;Lecuit, Thomas
通讯作者：
Lecuit, Thomas
DOI：
10.1073/pnas.0703033104
发表时间：
2007-05-22
影响因子：
11.1
作者：
Qian, Xiaolan;Li, Guorong;Lowy, Douglas R.
通讯作者：
Lowy, Douglas R.