ALCAM regulates motility, invasiveness, and adherens junction formation in uveal melanoma cells.
ALCAM regulates motility, invasiveness, and adherens junction formation in uveal melanoma cells.
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DOI：
10.1371/journal.pone.0039330
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Weiner JA
中科院分区：
文献类型：
--
作者：
Jannie KM;Stipp CS;Weiner JA
ALCAM是免疫球蛋白超家族的成员，与许多发育事件有关，并被反复鉴定为癌症转移的标志物。然而，以前关于ALCAM在癌症中的作用的研究产生了相互矛盾的结果。根据肿瘤细胞类型，文献中已报道ALCAM表达与癌症进展和转移呈正相关和负相关。为了更好地理解ALCAM如何调节癌细胞行为，我们利用了一组具有高或低ALCAM水平的确定的葡萄膜黑色素瘤细胞系，并使用多种测定直接测试了操纵这些水平对细胞运动性、侵袭性和粘附性的影响。在高ALCAM细胞系（MUM-2B）中，通过shRNA敲低稳定沉默ALCAM表达;所得细胞在间隙闭合试验中显示运动性降低，并通过transwell迁移试验测量侵袭性降低。免疫染色显示，沉默的细胞在粘附连接的形成中有缺陷，在粘附连接处，ALCAM与天然细胞中的N-钙粘蛋白和β-连环蛋白共定位。此外，我们在低ALCAM细胞系（MUM-2C）中稳定过表达ALCAM;有趣的是，这些细胞没有表现出运动性或侵袭性的任何增加，表明ALCAM是必要的，但不足以促进转移相关的细胞行为。然而，在这些ALCAM过表达的细胞中，β-连环蛋白和N-钙粘蛋白向粘附连接的募集增强。这些数据证实了先前提出的ALCAM在调节粘附连接中的作用，并且还提出了ALCAM可能差异性地增强或降低侵袭性的机制，这取决于原发性肿瘤周围组织中存在的钙粘蛋白粘附复合物的类型以及肿瘤细胞本身的钙粘蛋白状态。
ALCAM, a member of the immunoglobulin superfamily, has been implicated in numerous developmental events and has been repeatedly identified as a marker for cancer metastasis. Previous studies addressing ALCAM’s role in cancer have, however, yielded conflicting results. Depending on the tumor cell type, ALCAM expression has been reported to be both positively and negatively correlated with cancer progression and metastasis in the literature. To better understand how ALCAM might regulate cancer cell behavior, we utilized a panel of defined uveal melanoma cell lines with high or low ALCAM levels, and directly tested the effects of manipulating these levels on cell motility, invasiveness, and adhesion using multiple assays. ALCAM expression was stably silenced by shRNA knockdown in a high-ALCAM cell line (MUM-2B); the resulting cells displayed reduced motility in gap-closure assays and a reduction in invasiveness as measured by a transwell migration assay. Immunostaining revealed that the silenced cells were defective in the formation of adherens junctions, at which ALCAM colocalizes with N-cadherin and ß-catenin in native cells. Additionally, we stably overexpressed ALCAM in a low-ALCAM cell line (MUM-2C); intriguingly, these cells did not exhibit any increase in motility or invasiveness, indicating that ALCAM is necessary but not sufficient to promote metastasis-associated cell behaviors. In these ALCAM-overexpressing cells, however, recruitment of ß-catenin and N-cadherin to adherens junctions was enhanced. These data confirm a previously suggested role for ALCAM in the regulation of adherens junctions, and also suggest a mechanism by which ALCAM might differentially enhance or decrease invasiveness, depending on the type of cadherin adhesion complexes present in tissues surrounding the primary tumor, and on the cadherin status of the tumor cells themselves.
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影响因子：
8
作者：
Jeanes, A.;Gottardi, C. J.;Yap, A. S.
通讯作者：
Yap, A. S.
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
影响因子：
2.9
作者：
LAESSING, U;GIORDANO, S;STUERMER, CAO
通讯作者：
STUERMER, CAO
影响因子：
6.2
作者：
Bruder, SP;Ricalton, NS;Barry, FP
通讯作者：
Barry, FP
影响因子：
2.8
作者：
Kristiansen, G;Pilarsky, C;Rosenthal, A
通讯作者：
Rosenthal, A