A central role for cadherin signaling in cancer.
A central role for cadherin signaling in cancer.
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DOI：
10.1016/j.yexcr.2017.04.006
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发表时间：
2017-09-01
影响因子：
3.7
通讯作者：
Anastasiadis PZ
中科院分区：
文献类型：
--
作者：
Kourtidis A;Lu R;Pence LJ;Anastasiadis PZ
钙粘蛋白是一种嗜同性粘附分子，在细胞间粘附、组织形态发生和癌症中具有重要功能。在上皮细胞中，E-钙粘蛋白在细胞-细胞接触区域聚集，聚结成大分子复合物以形成粘附连接（AJs），并通过附属伴侣与皮质下肌动蛋白环缔合以形成顶端粘附小带（ZA）。作为上皮表型的主要调节因子，E-钙粘蛋白对于极化上皮单层的整体维持和稳态是必不可少的。其表达受与癌症相关的许多遗传和表观遗传机制调节，并且其功能受连接处的机械力、通过统称为连环蛋白的辅助蛋白的直接结合和磷酸化、通过内吞作用、再循环和降解以及通过多种信号传导途径和发育过程（如上皮向间充质转化（EMT））调节。由钙粘蛋白相关蛋白β-连环蛋白和p120介导的核信号传导促进生长、迁移和多能性。受体酪氨酸激酶、PI 3 K/AKT、Rho GT3和HIPPO信号传导均受E-钙粘蛋白介导的细胞-细胞粘附调节。最后，通过PLEKHA 7将微处理器复合物募集到ZA，以及随后对一小部分miRNA的调节提供了另外的机制，通过该机制，上皮细胞-细胞粘附的状态影响靶基因的翻译以维持极化上皮单层的稳态。总的来说，这些数据表明，E-钙粘蛋白功能的丧失，特别是在ZA，是癌症进展中常见和关键的一步。
Cadherins are homophilic adhesion molecules with important functions in cell-cell adhesion, tissue morphogenesis, and cancer. In epithelial cells, E-cadherin accumulates at areas of cell-cell contact, coalesces into macromolecular complexes to form the adherens junctions (AJs), and associates via accessory partners with a subcortical ring of actin to form the apical zonula adherens (ZA). As a master regulator of the epithelial phenotype, E-cadherin is essential for the overall maintenance and homeostasis of polarized epithelial monolayers. Its expression is regulated by a host of genetic and epigenetic mechanisms related to cancer, and its function is modulated by mechanical forces at the junctions, by direct binding and phosphorylation of accessory proteins collectively termed catenins, by endocytosis, recycling and degradation, as well as, by multiple signaling pathways and developmental processes, like the epithelial to mesenchymal transition (EMT). Nuclear signaling mediated by the cadherin associated proteins β-catenin and p120 promotes growth, migration and pluripotency. Receptor tyrosine kinase, PI3K/AKT, Rho GTPase, and HIPPO signaling, are all regulated by E-cadherin mediated cell-cell adhesion. Finally, the recruitment of the microprocessor complex to the ZA by PLEKHA7, and the subsequent regulation of a small subset of miRNAs provide an additional mechanism by which the state of epithelial cell-cell adhesion affects translation of target genes to maintain the homeostasis of polarized epithelial monolayers. Collectively, the data indicate that loss of E-cadherin function, especially at the ZA, is a common and crucial step in cancer progression.
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影响因子：
64.5
作者：
Drees, F;Pokutta, S;Weis, WI
通讯作者：
Weis, WI
影响因子：
37.3
作者：
Chao YL;Shepard CR;Wells A
通讯作者：
Wells A
影响因子：
64.8
作者：
Fischer KR;Durrans A;Lee S;Sheng J;Li F;Wong ST;Choi H;El Rayes T;Ryu S;Troeger J;Schwabe RF;Vahdat LT;Altorki NK;Mittal V;Gao D
通讯作者：
Gao D
影响因子：
21.3
作者：
Bertocchi C;Wang Y;Ravasio A;Hara Y;Wu Y;Sailov T;Baird MA;Davidson MW;Zaidel-Bar R;Toyama Y;Ladoux B;Mege RM;Kanchanawong P
通讯作者：
Kanchanawong P
影响因子：
3.9
作者：
Abba ML;Patil N;Leupold JH;Allgayer H
通讯作者：
Allgayer H