The protein kinase Akt induces epithelial mesenchymal transition and promotes enhanced motility and invasiveness of squamous cell carcinoma lines.
The protein kinase Akt induces epithelial mesenchymal transition and promotes enhanced motility and invasiveness of squamous cell carcinoma lines.
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发表时间：
2003-05
期刊：
影响因子：
11.2
通讯作者：
Sylvia Grille;A. Bellacosa;J. Upson;Andres J Klein-Szanto;F. van Roy;W. Lee‐Kwon;M. Donowitz;P. T
中科院分区：
文献类型：
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作者：
Sylvia Grille;A. Bellacosa;J. Upson;Andres J Klein-Szanto;F. van Roy;W. Lee‐Kwon;M. Donowitz;P. T
上皮-间充质转化(EMT)是上皮细胞发育和发生过程中的一个重要过程，通过该过程，上皮细胞获得成纤维细胞样属性，表现出细胞间黏附减少和运动能力增强。被设计为表达固有活性Akt的鳞状细胞癌细胞系接受了EMT，其特征是上皮标记物Desmoplakin、E-cadherin和β-catenin下调，而间质标志物vientin上调。细胞失去上皮细胞形态，获得成纤维细胞样特性。此外，E-钙粘蛋白在转录水平上下调。表达活性Akt的细胞减少了细胞间的粘附力，增加了纤维连接蛋白涂层表面的运动性，并增加了动物的侵袭性。AKT在许多人类肿瘤中被激活，AKT驱动的EMT可能提供组织侵袭和转移所需的运动性。这些发现表明，基于AKT抑制的未来疗法可能通过控制肿瘤细胞的侵袭和转移来补充传统疗法。
Epithelial-mesenchymal transition (EMT) is an important process during development and oncogenesis by which epithelial cells acquire fibroblast-like properties and show reduced intercellular adhesion and increased motility. Squamous cell carcinoma lines engineered to express constitutively active Akt underwent EMT, characterized by down-regulation of the epithelial markers desmoplakin, E-cadherin, and beta-catenin and up-regulation of the mesenchymal marker vimentin. The cells lost epithelial cell morphology and acquired fibroblast-like properties. Additionally, E-cadherin was down-regulated transcriptionally. The cells expressing constitutively active Akt exhibited reduced cell-cell adhesion, increased motility on fibronectin-coated surfaces, and increased invasiveness in animals. AKT is activated in many human carcinomas, and the AKT-driven EMT may confer the motility required for tissue invasion and metastasis. These findings suggest that future therapies based on AKT inhibition may complement conventional treatments by controlling tumor cell invasion and metastasis.