RRC ID 65119
Author Shiozaki A, Kudou M, Ichikawa D, Shimizu H, Arita T, Kosuga T, Konishi H, Komatsu S, Fujiwara H, Okamoto K, Kishimoto M, Marunaka Y, Otsuji E.
Title Expression and role of anion exchanger 1 in esophageal squamous cell carcinoma.
Journal Oncotarget
Abstract Recent studies have described important roles for the anion exchanger (AE) in epithelial carcinogenesis and tumor behavior. The objectives of the present study were to investigate the role of AE1 in the regulation of genes involved in tumor progression and the clinicopathological significance of its expression in esophageal squamous cell carcinoma (ESCC). An immunohistochemical analysis was performed on 61 primary tumor samples obtained from ESCC patients who underwent esophagectomy. AE1 was primarily located in the cell membranes or cytoplasm of carcinoma cells, and its distribution pattern was related to the histological degree of the differentiation of SCC or the pT category. Among patients with pT2-3 ESCC, the 5-year survival rate of patients with diffuse AE1 expression (40.2%) was significantly lower than that of patients with focal expression (74.0%). AE1 was strongly expressed in KYSE150 and TE8 human ESCC cells. The depletion of AE1 using siRNA inhibited cell proliferation, migration, and invasion and induced apoptosis. The results of the microarray analysis revealed that MAPK and Hedgehog signaling pathway-related genes, such as DHH, and GLI1, were down-regulated in AE1-depleted KYSE150 cells. In conclusions, the results of the present study suggest that the diffuse expression of AE1 is related to a worse prognosis in patients with advanced ESCC, and that it regulates tumor progression by affecting MAPK and Hedgehog signaling pathways. These results provide an insight into the role of AE1 as a mediator of and/or a biomarker for ESCC.
Volume 8(11)
Pages 17921-17935
Published 2017-3-14
DOI 10.18632/oncotarget.14900
PII 14900
PMID 28160546
PMC PMC5392297
MeSH Aged Anion Exchange Protein 1, Erythrocyte / biosynthesis Anion Exchange Protein 1, Erythrocyte / genetics* Anion Exchange Protein 1, Erythrocyte / metabolism Apoptosis / genetics Biomarkers, Tumor / genetics Carcinogenesis / genetics* Carcinoma, Squamous Cell / genetics* Carcinoma, Squamous Cell / mortality Carcinoma, Squamous Cell / pathology* Carcinoma, Squamous Cell / surgery Cell Line, Tumor Cell Movement / genetics Cell Proliferation / genetics Disease Progression Down-Regulation Esophageal Neoplasms / genetics* Esophageal Neoplasms / mortality Esophageal Neoplasms / pathology* Esophageal Neoplasms / surgery Esophageal Squamous Cell Carcinoma Esophagectomy Female Gene Expression Regulation, Neoplastic Hedgehog Proteins / biosynthesis Hedgehog Proteins / metabolism Humans Immunohistochemistry MAP Kinase Signaling System / genetics* Male Microarray Analysis Middle Aged Neoplasm Invasiveness / genetics Prognosis RNA Interference RNA, Small Interfering / genetics Survival Rate Zinc Finger Protein GLI1 / biosynthesis
IF 5.168
Human and Animal Cells TE-5(RCB1949) TE-8(RCB2098) TE-9(RCB1988) TE-15(RCB1951)