Feng Di, Yu Xiaoyu, Tian Xing, Meng Hongxue, Jiang Yang, Song HongTao, Li WenQi, Zhang HaoCheng, Geng Jingshu
Department of Pathology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang 150081, People's Republic of China.
Department of Microbiology and Center of Infectious Disease, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, People's Republic of China.
Cancer Manag Res. 2019 Oct 11;11:8911-8921. doi: 10.2147/CMAR.S221422. eCollection 2019.
Metadherin (MTDH), as an oncogene, is associated with metastasis and poor prognosis. This study investigated MTDH expressions and development of gastric cancer (GC) cell phenotypes and the contribution of MTDH to epithelial-mesenchymal transition (EMT).
MTDH expression was assayed in human GC cell lines and tumor tissue from 92 GC patients. Functional experiments were performed to characterize MTDH activity. Expressions of EMT-related proteins (vimentin and E-cadherin), phosphorylated β-catenin and β-catenin were assayed by immunohistochemistry, Western blotting, immunofluorescence, and co-immunoprecipitation, respectively.
MTDH expressions were higher in GC tissue than that in gastric mucosa from the same patient. MTDH overexpression was correlated with metastasis and enhanced malignant GC phenotypes, i.e., proliferation, migration, invasiveness, and chemoresistance. MTDH overexpression was associated with expressions of vimentin, E-cadherin and cancer stem-cell biomarkers including CD44, CD133, and Oct4. MTDH complexed with β-catenin and decreased phosphorylated β-catenin levels to facilitate β-catenin translocation into the nucleus and expressions of downstream genes.
MTDH overexpression in GC cells is associated with EMT and development of cancer stem cell malignant phenotypes and affects the subcellular translocation of β-catenin. The results warrant investigation of the prognostic value of MTDH in GC and as a therapeutic target.
作为一种癌基因，黏附素（MTDH）与转移和不良预后相关。本研究调查了MTDH在胃癌（GC）细胞中的表达、GC细胞表型的发展以及MTDH在上皮-间质转化（EMT）中的作用。
检测了人GC细胞系以及92例GC患者肿瘤组织中的MTDH表达。进行功能实验以表征MTDH活性。分别通过免疫组织化学、蛋白质印迹、免疫荧光和免疫共沉淀检测EMT相关蛋白（波形蛋白和E-钙黏蛋白）、磷酸化β-连环蛋白和β-连环蛋白的表达。
GC组织中MTDH的表达高于同一患者的胃黏膜组织。MTDH过表达与转移以及GC恶性表型增强相关，即增殖、迁移、侵袭和化疗耐药性增强。MTDH过表达与波形蛋白、E-钙黏蛋白以及癌症干细胞生物标志物（包括CD44、CD133和Oct4）的表达相关。MTDH与β-连环蛋白结合并降低磷酸化β-连环蛋白水平，以促进β-连环蛋白易位至细胞核并促进下游基因的表达。
GC细胞中MTDH过表达与EMT以及癌症干细胞恶性表型的发展相关，并影响β-连环蛋白的亚细胞易位。这些结果值得对MTDH在GC中的预后价值以及作为治疗靶点进行研究。
