A cell motility screen reveals role for MARCKS-related protein in adherens junction formation and tumorigenesis.
A cell motility screen reveals role for MARCKS-related protein in adherens junction formation and tumorigenesis.
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DOI：
10.1371/journal.pone.0007833
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发表时间：
2009-11-18
期刊：
影响因子：
3.7
通讯作者：
Freeman KW
中科院分区：
文献类型：
--
作者：
Finlayson AE;Freeman KW
通过细胞外基质（ECM）的侵袭对于伤口愈合、免疫应答和转移是重要的。我们建立了基于侵袭的细胞运动性筛选，使用覆盖有Matrigel的Boyden室来选择促侵袭基因。通过这种方法，我们鉴定了MARCKS相关蛋白（MRP）的反义核酸，MRP家族成员MARCKS是miR-21的靶点，miR-21是一种参与多种人类癌症中肿瘤生长、侵袭和转移的microRNA。我们证实，在EpRas乳腺上皮细胞和PC 3前列腺癌细胞中，MRP的靶向敲低促进了被三氟拉嗪阻断的体外细胞迁移。此外，我们观察到在MRP敲低的EpRas细胞中细胞-细胞接触位点处E-钙粘蛋白、β-连环蛋白和APC的免疫荧光增加，表明形成了粘附连接。通过伤口愈合测定，我们观察到降低的MRP支持集体细胞迁移，这是一种维持粘附连接的细胞运动。然而，不稳定的粘附连接，如在EpRas细胞中看到的那些，对于致癌信号传导通常是重要的。因此，敲低EpRas中的MRP导致体内肿瘤发生的丧失，并减少Wnt 3a诱导的体外TCF报告信号传导。总之，我们的数据表明，降低MRP表达促进EpRas细胞中粘附连接的形成，允许集体细胞迁移，但干扰致癌β-连环蛋白信号传导和肿瘤发生。
Invasion through the extracellular matrix (ECM) is important for wound healing, immunological responses and metastasis. We established an invasion-based cell motility screen using Boyden chambers overlaid with Matrigel to select for pro-invasive genes. By this method we identified antisense to MARCKS related protein (MRP), whose family member MARCKS is a target of miR-21, a microRNA involved in tumor growth, invasion and metastasis in multiple human cancers. We confirmed that targeted knockdown of MRP, in both EpRas mammary epithelial cells and PC3 prostate cancer cells, promoted in vitro cell migration that was blocked by trifluoperazine. Additionally, we observed increased immunofluoresence of E-cadherin, β-catenin and APC at sites of cell-cell contact in EpRas cells with MRP knockdown suggesting formation of adherens junctions. By wound healing assay we observed that reduced MRP supported collective cell migration, a type of cell movement where adherens junctions are maintained. However, destabilized adherens junctions, like those seen in EpRas cells, are frequently important for oncogenic signaling. Consequently, knockdown of MRP in EpRas caused loss of tumorigenesis in vivo, and reduced Wnt3a induced TCF reporter signaling in vitro. Together our data suggest that reducing MRP expression promotes formation of adherens junctions in EpRas cells, allowing collective cell migration, but interferes with oncogenic β-catenin signaling and tumorigenesis.
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影响因子：
8.8
作者：
通讯作者：
--
DOI：
10.1016/j.bbrc.2009.03.077
发表时间：
2009-06-05
影响因子：
3.1
作者：
Li, Tao;Li, Dong;Huang, Yiran
通讯作者：
Huang, Yiran
影响因子：
8
作者：
Macpherson, I. R.;Hooper, S.;Brunton, V. G.
通讯作者：
Brunton, V. G.
影响因子：
7.5
作者：
Gimona, Mario;Buccione, Roberto;Linder, Stefan
通讯作者：
Linder, Stefan
DOI：
10.1083/jcb.200209006
发表时间：
2003-01-20
期刊：
The Journal of cell biology
影响因子：
--
作者：
Wolf K;Mazo I;Leung H;Engelke K;von Andrian UH;Deryugina EI;Strongin AY;Bröcker EB;Friedl P
通讯作者：
Friedl P