Expression and role of anion exchanger 1 in esophageal squamous cell carcinoma
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Atsushi Shiozaki1,*, Michihiro Kudou1,*, Daisuke Ichikawa1, Hiroki Shimizu1, Tomohiro Arita1, Toshiyuki Kosuga1, Hirotaka Konishi1, Shuhei Komatsu1, Hitoshi Fujiwara1, Kazuma Okamoto1, Mitsuo Kishimoto2, Yoshinori Marunaka3,4, Eigo Otsuji1
1Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, 602-8566, Japan
2Department of Pathology, Kyoto Prefectural University of Medicine, Kyoto, 602-8566, Japan
3Department of Molecular Cell Physiology and Bio-Ionomics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, 602-8566, Japan
4Japan Institute for Food Education and Health, St. Agnes’ University, Kyoto, 602-8013, Japan
*These authors have contributed equally to this work
Atsushi Shiozaki, email: firstname.lastname@example.org
Keywords: AE1, esophageal squamous cell carcinoma, MAPK, Hedgehog signaling pathway, cellular physiology
Received: April 20, 2016 Accepted: January 04, 2017 Published: January 30, 2017
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.
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