FAT1 prevents epithelial mesenchymal transition (EMT) via MAPK/ERK signaling pathway in esophageal squamous cell cancer
FAT1 prevents epithelial mesenchymal transition (EMT) via MAPK/ERK signaling pathway in esophageal squamous cell cancer
复制标题
FAT1通过MAPK/ERK信号通路阻止食管鳞状细胞癌中的上皮间质转化（EMT）
DOI：
10.1016/j.canlet.2017.03.033
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发表时间：
2017-07-01
期刊：
影响因子：
9.7
通讯作者：
Cui, Yongping
中科院分区：
文献类型：
--
作者：
Hu, Xiaoling;Zhai, Yuanfang;Cui, Yongping
FAT 1在人类癌症中作为癌基因或肿瘤抑制因子调节细胞-细胞粘附、细胞生长、细胞迁移和肌动蛋白动力学。FAT 1基因是食管鳞状细胞癌（esophageal squamous cell carcinoma，ESCC）中一个重要的突变基因。然而，FAT 1在食管鳞癌中的作用及其可能机制尚不清楚。在这项研究中，我们报告，FAT 1的表达显着降低在食管鳞癌肿瘤组织。FAT 1的外源性表达导致细胞增殖和集落形成的抑制，以及细胞的迁移和侵袭，而FAT 1敲低在体外和体内显示相反的趋势。此外，FAT 1敲低导致E-cadherin表达的统计学降低和N-cadherin、Vimentin和Snail的表达以IVIAPK/ERK途径依赖的方式显著增加。而FAT 1的过度表达则导致相反的趋势。这些改变在MEK特异性抑制剂U 0126的存在下被废除。总的来说，我们的研究确定了FAT 1在抑制ESCC中肿瘤生长和EMT发生中的新作用。我们认为FAT 1对MAPK/ERK通路的破坏有助于ESCC的EMT，对理解ESCC的发展具有重要意义。(C)2017爱思唯尔B. V.保留所有权利。
FAT1 regulates cell-cell adhesion, cell growth, cell migration, and actin dynamics as either oncogene or tumor suppressor in human cancers. We previously identified FAT1 was one of significant mutant genes in esophageal squamous cell carcinoma (ESCC). However, the function and underlying mechanism of FAT1 in ESCC have not been explored. In this study, we report that FAT1 expression was significantly lower in ESCC tumor tissues. Exogenous expression of FAT1 led to inhibition of cell proliferation and colony formation, as well as cell migration and invasion whereas FAT1 knockdown showed the opponent trends in vitro and in vivo. Moreover, FAT1 knockdown led to a statistically decrease of E-cadherin expression and a dramatically increase expression of N-cadherin, Vimentin, and Snail in a IVIAPK/ERK pathway-dependent manner. Meanwhile, over-expression of FAT1 resulted in the opposite trends. These alterations were abrogated in the presence of U0126, a MEK specific inhibitor. Collectively, our studies identified a novel role for FAT1 in inhibiting tumor growth and EMT occurrence in ESCC. We proposed that disruption of MAPK/ERK pathway by FAT1 contributes the EMT in ESCC and has important implications for understanding ESCC development. (C) 2017 Elsevier B.V. All rights reserved.