Amplification and overexpression of CTTN (EMS1) contribute to the metastasis of esophageal squamous cell carcinoma by promoting cell migration and anoikis resistance
Amplification and overexpression of CTTN (EMS1) contribute to the metastasis of esophageal squamous cell carcinoma by promoting cell migration and anoikis resistance
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DOI：
10.1158/0008-5472.can-06-1484
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发表时间：
2006-12-15
期刊：
影响因子：
11.2
通讯作者：
Wang, Ming-Rong
中科院分区：
文献类型：
--
作者：
Luo, Man-Li;Shen, Xiao-Ming;Wang, Ming-Rong
染色体11q13的获得是食管鳞状细胞癌（ESCC）的常见事件。位于11q13的皮质蛋白基因（CTTN，也称为EMS）在将膜动力学耦合到皮质肌动蛋白组装中起关键作用。该基因与几种类型细胞的运动有关。在本研究中，我们发现CTTN基因的扩增和过表达与食管鳞癌的淋巴结转移有关。通过小干扰RNA介导的CTTN沉默的功能分析显示，除了对细胞迁移的影响外，CTTN还通过抗失巢凋亡影响细胞侵袭力。体内实验表明，CTTN表达的抑制也降低了ESCC细胞的肿瘤生长和肺转移。在分子水平上，我们首次发现CTTN在抗失巢凋亡中的保护作用与磷脂酰肌醇3-激酶/Akt通路的激活相关。总的来说，数据表明CTTN是11q13扩增子中的癌基因，并在ESCC的肿瘤转移中发挥作用。
Gain of chromosome 11q13 is a common event in esophageal squamous cell carcinoma (ESCC). The cortactin gene (CTTN, also EMS]), located at 11q13, plays a pivotal role in coupling membrane dynamics to cortical actin assembly. This gene has been implicated in the motility of several types of cells. In the present study, we found that the amplification and overexpression of the CTTN gene was associated with lymph node metastasis in ESCC. Functional analysis by small interfering RNA-mediated silencing of CTTN revealed that in addition to the effect on cell migration, CTTN influenced cell invasiveness by anoikis resistance. In vivo assay showed that inhibition of CTTN expression also decreased tumor growth and lung metastasis of ESCC cells. At the molecular level, we showed for the first time that the protective role of CTTN in anoikis resistance was correlated with the activation of the phosphatidylinositol 3-kinase/Akt pathway. Overall, the data suggest that CTTN is an oncogene in the 11q13 amplicon and exerts functions on tumor metastasis in ESCC.