机构:[1]Department of Thoracic Surgery, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China临床科室胸心外科(胸外科 心脏血管外科)河北医科大学第四医院[2]Thoracic Oncology Program, Department of Surgery, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94115, USA[3]Department of Respiratory Diseases, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang 310016[4]Department of Pharmacology, Medical College of Jiaxing University, Jiaxing, Zhejiang 314000[5]Department of Biotechnology and Biomedicine, Zhejiang Provincial Key Laboratory of Applied Enzymology and Jiaxing ACCB Diagnostics, Yangze Delta Region Institute of Tsinghua University Zhejiang, Jiaxing, Zhejiang 314006, P.R. China
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.
基金:
Eileen D. Ludwig Endowed Fund for Thoracic Oncology Research; Science and Technology Support Project of Hebei Province [132077127D]; Fund for International Scientific and Technological Cooperation in Hebei Province [18397771D]; Fund for Scientific and Technological Activities of Overseas Scholars by Hebei Provincial Office of Human and Social Affairs [CY201613]; Science and Technology Planning Project of Zhejiang Province Science and Technology Department [2018C37091]; Zhejiang Provincial Natural Science Foundation of ChinaNatural Science Foundation of Zhejiang Province [LY15H160048]; Jiaxing Science and Technology Project [2015BZ12001]; Jiaxing Nanhu District Science and Technology Project [2018QC03]
第一作者机构:[1]Department of Thoracic Surgery, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China[2]Thoracic Oncology Program, Department of Surgery, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94115, USA
共同第一作者:
通讯作者:
通讯机构:[4]Department of Pharmacology, Medical College of Jiaxing University, Jiaxing, Zhejiang 314000[5]Department of Biotechnology and Biomedicine, Zhejiang Provincial Key Laboratory of Applied Enzymology and Jiaxing ACCB Diagnostics, Yangze Delta Region Institute of Tsinghua University Zhejiang, Jiaxing, Zhejiang 314006, P.R. China[*1]Department of Pharmacology, Medical College of Jiaxing University, Jiaxing, Zhejiang 314000, P.R. China[*2]Department of Biotechnology and Biomedicine, Zhejiang Provincial Key Laboratory of Applied Enzymology, Yangze Delta Region Institute of Tsinghua University Zhejiang and ACCB Diagnostics, Jiaxing, Zhejiang 314006, P.R. China
推荐引用方式(GB/T 7714):
Wang Lei,Jin Joy,Zhou Yong,et al.EMX2 is epigenetically silenced and suppresses epithelial-mesenchymal transition in human esophageal adenocarcinoma[J].ONCOLOGY REPORTS.2019,42(5):2169-2178.doi:10.3892/or.2019.7284.
APA:
Wang, Lei,Jin, Joy,Zhou, Yong,Tian, Ziqiang,He, Biao...&Ding, Feng.(2019).EMX2 is epigenetically silenced and suppresses epithelial-mesenchymal transition in human esophageal adenocarcinoma.ONCOLOGY REPORTS,42,(5)
MLA:
Wang, Lei,et al."EMX2 is epigenetically silenced and suppresses epithelial-mesenchymal transition in human esophageal adenocarcinoma".ONCOLOGY REPORTS 42..5(2019):2169-2178