Type II transglutaminase stimulates epidermal cancer stem cell epithelial-mesenchymal transition.
Type II transglutaminase stimulates epidermal cancer stem cell epithelial-mesenchymal transition.
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DOI：
10.18632/oncotarget.3890
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发表时间：
2015-08-21
期刊：
影响因子：
--
通讯作者：
Eckert RL
中科院分区：
文献类型：
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作者：
Fisher ML;Adhikary G;Xu W;Kerr C;Keillor JW;Eckert RL
II型转氨酶（TG 2）是一种多功能蛋白质，最近被认为在ECS细胞存活中起作用。在本研究中，我们调查TG 2在调节ECS细胞的上皮间质转化（EMT）中的作用。我们的研究表明，TG 2敲低或用TG 2抑制剂处理，导致EMT标志物表达减少，细胞迁移和侵袭减少。TG 2具有多种活性，但最突出的是其转酰胺酶和GTP结合活性。对一系列TG 2突变体的分析表明，TG 2 GTP结合活性，而不是转酰胺酶活性，是表达EMT标志物（Twist、Snail、Slug、波形蛋白、纤连蛋白、N-钙粘蛋白和HIF-1α）以及增加ECS细胞侵袭和迁移所必需的。这与E-cadherin的表达减少相结合。另外的研究表明，NF-κ B B信号传导，其被认为是介导TG 2对乳腺癌细胞中EMT的影响，但不参与皮肤癌中EMT的TG 2调节。这些研究表明，TG 2是维持ECS细胞EMT、侵袭和迁移所必需的，并表明抑制TG 2 GTP结合/G蛋白相关活性可降低皮肤癌肿瘤存活率。
Type II transglutaminase (TG2) is a multifunctional protein that has recently been implicated as having a role in ECS cell survival. In the present study we investigate the role of TG2 in regulating epithelial mesenchymal transition (EMT) in ECS cells. Our studies show that TG2 knockdown or treatment with TG2 inhibitor, results in a reduced EMT marker expression, and reduced cell migration and invasion. TG2 has several activities, but the most prominent are its transamidase and GTP binding activity. Analysis of a series of TG2 mutants reveals that TG2 GTP binding activity, but not the transamidase activity, is required for expression of EMT markers (Twist, Snail, Slug, vimentin, fibronectin, N-cadherin and HIF-1α), and increased ECS cell invasion and migration. This coupled with reduced expression of E-cadherin. Additional studies indicate that NF&#ξ03BA;B signaling, which has been implicated as mediating TG2 impact on EMT in breast cancer cells, is not involved in TG2 regulation of EMT in skin cancer. These studies suggest that TG2 is required for maintenance of ECS cell EMT, invasion and migration, and suggests that inhibiting TG2 GTP binding/G-protein related activity may reduce skin cancer tumor survival.