Department of Thoracic Surgery, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China.
Thoracic Oncology Program, Department of Surgery, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94115, USA.
Oncol Rep. 2019 Nov;42(5):2169-2178. doi: 10.3892/or.2019.7284. Epub 2019 Aug 20.
Esophageal adenocarcinoma (EAC) is an aggressive and challenging disease to treat, with an overall five‑year survival rate of <20%. Early malignant cell dissemination contributes to this poor prognosis. Epithelial‑mesenchymal transition (EMT) induces the invasion and metastasis of carcinoma cells. Empty spiracles homeobox 2 (EMX2) is a homeodomain‑containing transcription factor, which is associated with numerous cancer types, and has been demonstrated to regulate EMT. In the present study, 48 pairs of EAC and adjacent normal tissues were analyzed. The results revealed that EMX2 was downregulated in EAC tissues, and its expression was negatively correlated with the DNA hypermethylation of its promoter. Additionally, the OE19 and OE33 EAC cell lines were treated with the DNA methyltransferase inhibitor 5‑aza‑2'‑deoxycytidine, and the results indicated that EMX2 expression was increased. Overexpressing EMX2 in EAC cell lines enhanced the expression of apoptotic markers, inhibited cell migration and invasion, led to the upregulation of E‑cadherin and the downregulation of mesenchymal markers, and suppressed AKT, mTOR and S6K phosphorylation. Furthermore, EMX2 overexpression sensitized EAC cells to cisplatin. These results demonstrated that EMX2 inhibited the AKT/mTOR/S6K signaling pathway and decreased EMT. However, the downregulation of EMX2 was revealed to be associated with EMT in EAC, indicating that EMX2 may be a potential target for the management of EAC.
食管腺癌 (EAC) 是一种难以治疗的侵袭性疾病，整体五年生存率<20%。早期恶性细胞扩散导致了这种不良预后。上皮-间充质转化 (EMT) 诱导癌细胞的侵袭和转移。空泡同源盒 2 (EMX2) 是一种含同源域的转录因子，与多种癌症类型相关，并已被证明可调节 EMT。在本研究中，分析了 48 对 EAC 和相邻正常组织。结果表明，EMX2 在 EAC 组织中下调，其表达与启动子的 DNA 高甲基化呈负相关。此外，OE19 和 OE33 EAC 细胞系用 DNA 甲基转移酶抑制剂 5-aza-2'-脱氧胞苷处理，结果表明 EMX2 表达增加。在 EAC 细胞系中过表达 EMX2 可增强凋亡标志物的表达，抑制细胞迁移和侵袭，导致 E-钙黏蛋白上调和间充质标志物下调，并抑制 AKT、mTOR 和 S6K 磷酸化。此外，EMX2 的过表达使 EAC 细胞对顺铂敏感。这些结果表明，EMX2 抑制了 AKT/mTOR/S6K 信号通路并减少了 EMT。然而，EMX2 的下调与 EAC 中的 EMT 有关，表明 EMX2 可能是 EAC 管理的潜在靶点。
