Junctional recruitment of mammalian Scribble relies on E-cadherin engagement
Junctional recruitment of mammalian Scribble relies on E-cadherin engagement
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DOI：
10.1038/sj.onc.1208632
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发表时间：
2005-06-01
期刊：
影响因子：
8
通讯作者：
Borg, JP
中科院分区：
文献类型：
--
作者：
Navarro, C;Nola, S;Borg, JP
LAP蛋白家族的成员，秀丽隐杆线虫的LET-413，黑腹果蝇的Scribble，哺乳动物的Erbin， Lano， Densin-180和hScrib，具有保守的结构特征。LET-413和Scribble是参与建立和维持上皮细胞极性的连接蛋白。Scribble也可以作为肿瘤抑制基因。我们在这里表明，在上皮细胞中，hScrib以依赖E-cadherin的方式在细胞-细胞连接处募集，如MDCK细胞中的钙开关实验、5-Aza-2'-脱氧胞苷（5Aza）处理的MDA-231细胞中E-cadherin的重新表达和siRNA实验所示。hScrib受其LRR结构域限制在上皮细胞的基底外侧膜上，并在Triton x -100不溶性组分中富集。在乳腺癌中，大多数小叶肿瘤不表达hScrib和E-cadherin，而导管肿瘤hScrib下调的频率较低。我们的数据为细胞-细胞连接处募集hScrib的方式提供了额外的见解，并建立了E-cadherin和hScrib肿瘤抑制因子之间的潜在联系。
Members of the LAP protein family, LET-413 in Caenorhabditis elegans, Scribble in Drosophila melanogaster, and Erbin, Lano, Densin-180 and hScrib in mammals, have conserved structural features. LET-413 and Scribble are junctional proteins involved in establishing and maintaining epithelial cell polarity. scribble also behaves as a neoplastic tumor suppressor gene. We show here that, in epithelial cells, hScrib is recruited at cell-cell junctions in an E-cadherin-dependent manner as shown by calcium switch assays in MDCK cells, re-expression of E-cadherin in MDA-231 cells treated by 5-Aza-2'-deoxycytidine (5Aza), and siRNA experiments. hScrib is restricted at the basolateral membrane of epithelial cells by its LRR domain, and is enriched in Triton X-100-insoluble fractions. In breast cancers, most lobular tumors did not express hScrib and E-cadherin while ductal tumors had a less frequent downregulation of hScrib. Our data provide additional insights on the modalities of recruitment of hScrib at the cell-cell junctions, and establish a potential link between the E-cadherin and hScrib tumor suppressors.