Down-regulation of programmed cell death 4 leads to epithelial to mesenchymal transition and promotes metastasis in mice.
Down-regulation of programmed cell death 4 leads to epithelial to mesenchymal transition and promotes metastasis in mice.
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DOI：
10.1016/j.ejca.2012.12.014
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发表时间：
2013-05
影响因子：
8.4
通讯作者：
Yang, Hsin-Sheng
中科院分区：
文献类型：
--
作者：
Wang, Qing;Zhu, Jiang;Zhang, Yong;Sun, Zhenxiao;Guo, Xiaoling;Wang, Xin;Lee, Eun;Bakthavatchalu, Vasudevan;Yang, Qifeng;Yang, Hsin-Sheng
在这项研究中，我们证明，敲低程序性细胞死亡4（Pdcd 4），一种新的肿瘤抑制因子，在体外和体内，减少上皮特异性蛋白的表达，并增加间充质特异性蛋白的表达，这表明Pdcd 4敲低导致上皮间质转化（EMT）。敲低Pdcd 4分别增加了伤口愈合试验和Boyden室迁移试验中的伤口闭合速率和迁移能力，表明Pdcd 4敲低促进了细胞迁移。Pdcd 4敲除也改变了GEO细胞对细胞外基质的粘附能力，包括层粘连蛋白、胶原IV和纤连蛋白。为了测试Pdcd 4的敲低是否促进体内转移，将亲本、对照和Pdcd 4敲低细胞注射到裸鼠的盲肠壁（原位植入）中。在所有注射的小鼠中，在盲肠上形成肿瘤。然而，只有注射Pdcd 4敲低细胞的小鼠发生肝和局部淋巴结转移。免疫组织化学染色分析显示，c-Myc和Snail/Slug表达上调肿瘤注射Pdcd 4敲低细胞。这些结果表明，通过Pdcd 4敲低促进转移是由c-Myc和Snail/Slug在裸鼠中的上调贡献的。总之，我们的数据表明，敲低Pdcd 4导致EMT，粘附的改变，促进迁移和转移。
In this study, we demonstrated that knockdown of Programmed cell death 4 (Pdcd4), a novel tumor suppressor, decreased the expressions of epithelial-specific proteins and increased the expressions of mesenchymal-specific proteins in vitro and in vivo, suggesting that knockdown of Pdcd4 results in epithelial to mesenchymal transition (EMT). Knockdown of Pdcd4 increased the rate of wound closure and migration capacity in wound-healing assays and Boyden chamber migration assays, respectively, indicating that Pdcd4 knockdown promotes cell migration. Pdcd4 knockdown also altered the adhesion capacity of GEO cells to extracellular matrix including laminin, collagen IV, and fibronectin. To test whether knockdown of Pdcd4 promotes metastasis in vivo, parental, control, and Pdcd4 knockdown cells were injected into the cecal wall (orthotopic implantation) of nude mice. Tumors are formed on cecum in all injected mice. However, only mice injected with Pdcd4 knockdown cells developed hepatic and local lymph node metastases. Immunohistochemical staining analyses showed that c-Myc and Snail/Slug expressions were up-regulated in the tumors from injection with Pdcd4 knockdown cells. These results implicated that promotion of metastasis by Pdcd4 knockdown was contributed by up-regulation of c-Myc and Snail/Slug in nude mice. Taken together, our data demonstrated that knockdown of Pdcd4 leads to EMT, alternation of adhesion, and promotion of migration and metastasis.
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DOI：
10.1073/pnas.96.24.14037
发表时间：
1999-11-23
影响因子：
11.1
作者：
Cmarik, JL;Min, HZ;Colburn, NH
通讯作者：
Colburn, NH
影响因子：
21.3
作者：
Batlle, E;Sancho, E;de Herreros, AG
通讯作者：
de Herreros, AG
影响因子：
4
作者：
Bolós, V;Peinado, H;Cano, A
通讯作者：
Cano, A
影响因子：
11.2
作者：
Hulit, James;Suyama, Kimita;Hazan, Rachel B.
通讯作者：
Hazan, Rachel B.
影响因子：
6.2
作者：
Mudduluru, Giridhar;Medved, Fabian;Allgayer, Heike
通讯作者：
Allgayer, Heike