Tumor suppressor CADM1 is involved in epithelial cell structure
Tumor suppressor CADM1 is involved in epithelial cell structure
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DOI：
10.1016/j.bbrc.2009.10.088
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发表时间：
2009-12-18
影响因子：
3.1
通讯作者：
Murakami, Yoshinori
中科院分区：
文献类型：
--
作者：
Sakurai-Yageta, Mika;Masuda, Mari;Murakami, Yoshinori
肿瘤抑制因子CADM 1参与细胞粘附，并在浸润性癌症中优先失活。我们以前报道过CADM 1与肌动蛋白结合蛋白4.1 B/DAL-1和支架蛋白棕榈酰化膜蛋白3（MPP 3）/DLG 3相关。然而，CADM 1抑制肿瘤的潜在机制尚未阐明。在这里，我们证明了MPP 1/p55和MPP 2/DLG 2，以及MPP 3，与CADM 1和4.1 B相互作用，形成三方复合物。然后，我们使用HEK 293细胞研究了CADM 1及其复合物在上皮中的细胞生物学作用。在MPP 1 -3中，MPP 2在HEK 293细胞中粘附的早期过程中被募集到CADM 1 -4.1B复合物。通过使用siRNA抑制CADM 1表达，HEK 293失去上皮样结构并显示具有未成熟细胞粘附的平坦形态。4.1 B和MPP 2以及E-钙粘蛋白和ZO-1通过HEK 293中CADM 1的耗尽而从膜错误定位。在几种缺乏CADM 1表达的具有转化形态的癌细胞中也观察到MPP 2的错误定位。这些发现表明，CADM 1与4.1B和MPP 2一起参与上皮样细胞结构的形成，而其功能的丧失可能导致癌细胞的形态转化。(C)2009爱思唯尔公司All rights reserved.
The tumor suppressor, CADM1, is involved in cell adhesion and preferentially inactivated in invasive cancer. We have previously reported that CADM1 associates with an actin-binding protein, 4.1 B/DAL-1, and a scaffold protein, membrane protein palmitoylated 3 (MPP3)/DLG3. However, underlying mechanism of tumor suppression by CADM1 is not clarified yet. Here, we demonstrate that MPP1/p55 and MPP2/DLG2, as well as MPP3, interact with both CADM1 and 4.1 B, forming a tripartite complex. We then examined cell biological roles of CADM1 and its complex in epithelia using HEK293 cells. Among MPP1-3, MPP2 is recruited to the CADM1-4.1B complex in the early process of adhesion in HEK293 cells. By suppression of CADM1 expression using siRNA, HEK293 lose epithelia-like structure and show flat morphology with immature cell adhesion. 4.1 B and MPP2, as well as E-cadherin and ZO-1, are mislocalized from the membrane by depletion of CADM1 in HEK293. Mislocalization of MPP2 is also observed in several cancer cells lacking CADM1 expression with the transformed morphology. These findings suggest that CADM1 is involved in the formation of epithelia-like cell structure with 4.1B and MPP2, while loss of its function could cause morphological transformation of cancer cells. (C) 2009 Elsevier Inc. All rights reserved.