title: The metastasis-associated gene MTA3, a component of the Mi-2/NuRD transcriptional repression complex, predicts prognosis of gastroesophageal junction adenocarcinoma.
abstract: Gastroesophageal junction (GEJ) adenocarcinoma carries a poor prognosis that is largely attributable to early and frequent metastasis. The acquisition of metastatic potential in cancer involves epithelial-to-mesenchymal transition (EMT). The metastasis-associated gene MTA3, a novel component of the Mi-2/NuRD transcriptional repression complex, was identified as master regulator of EMT through inhibition of Snail to increase E-cadherin expression in breast cancer. Here, we evaluated the expression pattern of the components of MTA3 pathway and the corresponding prognostic significance in GEJ adenocarcinoma. MTA3 expression was decreased at both protein and mRNA levels in tumor tissues compared to the non-tumorous and lowed MTA3 levels were noted in tumor cell lines with stronger metastatic potential. Immunohistochemical analysis of a cohort of 128 cases exhibited that patients with lower expression of MTA3 had poorer outcomes. Combined misexpression of MTA3, Snail and E-cadherin had stronger correlation with malignant properties. Collectively, results suggest that the MTA3-regulated EMT pathway is altered to favor EMT and, therefore, disease progression and that MTA3 expression was an independent prognostic factor in patients with GEJ adenocarcinoma.
authors.affiliation: Department of Integrative Oncology, Affiliated Cancer Hospital of Shantou University Medical College, Shantou, China.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Dong
authors.forename: Hong
authors.initials: H
authors.lastname: Guo
authors.forename: Liangxi
authors.initials: L
authors.lastname: Xie
authors.forename: Geng
authors.initials: G
authors.lastname: Wang
authors.forename: Xueyun
authors.initials: X
authors.lastname: Zhong
authors.forename: Thaer
authors.initials: T
authors.lastname: Khoury
authors.forename: Dongfeng
authors.initials: D
authors.lastname: Tan
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D004943:Esophagogastric Junction / Q000473:pathology*; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000071250:Snail Family Transcription Factors; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D014408:Biomarkers, Tumor; C513384:CDH1 protein, human; D015820:Cadherins; C486657:MTA3 protein, human; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors