EphA3 inhibits migration and invasion of esophageal cancer cells by activating the mesenchymal-epithelial transition process
EphA3 inhibits migration and invasion of esophageal cancer cells by activating the mesenchymal-epithelial transition process
复制标题
EphA3通过激活间充质-上皮转化过程抑制食管癌细胞的迁移和侵袭
DOI：
10.3892/ijo.2018.4639
复制
发表时间：
2019-02-01
影响因子：
5.2
通讯作者：
Li, Jian-Zhong
中科院分区：
文献类型：
--
作者：
Chen, Xia;Lu, Bin;Li, Jian-Zhong
在正常和致癌发育过程中，Eph受体酪氨酸激酶对细胞间通讯至关重要。Eph受体A3 （EphA3）的表达与某些类型癌症的肿瘤促进有关；然而，它在其他肿瘤中起抑制作用。应用逆转录-定量聚合酶链式反应和Transwell侵袭试验检测食管鳞癌（ESCC）细胞株中EphA3的表达水平及其对肿瘤进展的影响。本研究表明EphA3在ESCC组织和细胞系中表达降低。DNA甲基化抑制剂5-aza-2′-脱氧胞苷处理可提高ESCC细胞系KYSE510和KYSE30中EphA3 mRNA的表达水平。此外，在KYSE450和KYSE510细胞中过表达EphA3可抑制细胞迁移和侵袭。EphA3过表达也降低了RhoA GTPase。此外，EphA3过表达诱导间充质-上皮转化，表现为上皮样形态学改变，上皮蛋白（E-cadherin和紧密连接蛋白1 occludens-1）表达增加，间充质蛋白（Vimentin， N-cadherin和Snail）表达减少。相反，在KYSE410细胞中沉默EphA3可触发上皮-间质转化，促进细胞迁移和侵袭。这些结果提示EphA3可能在ESCC中发挥肿瘤抑制作用。
Eph receptor tyrosine kinases are critical for cell-cell communication during normal and oncogenic development. Eph receptor A3 (EphA3) expression is associated with tumor promotion in certain types of cancer; however, it acts as a tumor suppressor in others. The expression levels of EphA3 and its effects on tumor progression in esophageal squamous cell carcinoma (ESCC) cell lines were determined using reverse transcription-quantitative polymerase chain reaction analysis and a Transwell invasion assay. The present study demonstrated that EphA3 expression was decreased in ESCC tissues and cell lines. Treatment with the DNA methylation inhibitor 5-aza-2'-deoxycytidine increased the mRNA expression levels of EphA3 in the ESCC cell lines KYSE510 and KYSE30. In addition, overexpression of EphA3 in KYSE450 and KYSE510 cells inhibited cell migration and invasion. EphA3 overexpression also decreased RhoA GTPase. Furthermore, EphA3 overexpression induced mesenchymal-epithelial transition, as demonstrated by epithelial-like morphological alterations, increased expression of epithelial proteins (E-cadherin and the tight junction protein 1 zonula occludens-1) and decreased expression of mesenchymal proteins (Vimentin, N-cadherin and Snail). Conversely, silencing EphA3 in KYSE410 cells triggered epithelial-mesenchymal transition, and promoted cell migration and invasion. These results suggested that EphA3 may serve a tumor-suppressor role in ESCC.