Mammalian Eps15 homology domain 1 promotes metastasis in non-small cell lung cancer by inducing epithelial-mesenchymal transition.
Mammalian Eps15 homology domain 1 promotes metastasis in non-small cell lung cancer by inducing epithelial-mesenchymal transition.
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哺乳动物Eps15同源结构域1通过诱导上皮间质转化促进非小细胞肺癌转移
DOI：
10.18632/oncotarget.11220
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发表时间：
2017-04-04
期刊：
影响因子：
--
通讯作者：
Cai L
中科院分区：
文献类型：
--
作者：
Meng Q;Xing Y;Ren T;Lu H;Xi Y;Jiang Z;Hu J;Li C;Sun L;Sun D;Cai L
确定导致非小细胞肺癌（NSCLC）转移性扩散的最早分子事件对于早期检测、预防和治疗干预仍然至关重要。在这项研究中，我们假设哺乳动物Eps 15同源结构域1（EHD 1）可能是负责在NSCLC细胞的转移行为。我们证实EHD 1的上调与NSCLC患者的淋巴结转移和不利的生存相关。EHD 1基因敲低抑制了人NSCLC细胞的侵袭和迁移，而EHD 1基因过表达增加了肺癌细胞的转移潜能。使用Affyscore Human Gene 1.0 ST平台，微阵列分析揭示了EHD 1与上皮-间充质转化（EMT）之间的关联，这得到了细胞系中EHD 1敲低后间充质标志物下调和上皮标志物上调的支持。此外，EHD 1的过表达诱导EMT，并增加肺癌细胞在体外和体内的转移潜力。这些结果为阐明EHD 1表达与肺癌转移的关系提供了一个模型，为肺癌的预后和治疗开辟了新的途径。
The identification of the earliest molecular events responsible for the metastatic dissemination of non-small cell lung cancer (NSCLC) remains critical for early detection, prevention, and treatment interventions. In this study, we hypothesized that Mammalian Eps15 homology domain 1 (EHD1) might be responsible for the metastatic behavior of cells in NSCLC. We demonstrated that upregulation of EHD1 is associated with lymph nodes metastasis and unfavorable survival in patients with NSCLC. EHD1 knockdown inhibited the invasion and migration of human NSCLC cells, and overexpression of EHD1 increased the metastatic potential of lung cancer cells. Using the Affymetrix Human Gene 1.0 ST platform, microarray analysis revealed that an association between EHD1 and epithelial-mesenchymal transition (EMT), supported by downregulation of mesenchymal markers and upregulation of epithelial markers following knockdown of EHD1 in cell lines. Moreover, overexpression of EHD1 induced the EMT and increased the metastatic potential of lung cancer cells in vitro and in vivo. These results provide a model to illustrate the relationship between EHD1 expression and lung cancer metastasis, opening up new avenues for the prognosis and therapy of lung cancer.