Aquaporin 1 suppresses apoptosis and affects prognosis in esophageal squamous cell carcinoma
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Yuzo Yamazato1,*, Atsushi Shiozaki1,*, Daisuke Ichikawa1,2, Toshiyuki Kosuga1, Katsutoshi Shoda1, Tomohiro Arita1, Hirotaka Konishi1, Shuhei Komatsu1, Takeshi Kubota1, Hitoshi Fujiwara1, Kazuma Okamoto1, Mitsuo Kishimoto3, Eiichi Konishi3, Yoshinori Marunaka4,5 and Eigo Otsuji1
1Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, 602-8566, Japan
2Department of Gastrointestinal, Breast & Endocrine Surgery, Faculty of Medicine, University of Yamanashi, Chuo, 409-3898, Japan
3Department of Pathology, Kyoto Prefectural University of Medicine, Kyoto, 602-8566, Japan
4Departments of Molecular Cell Physiology and Bio-Ionomics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, 602-8566, Japan
5Japan Institute for Food Education and Health, St. Agnes’ University, Kyoto, 602-8013, Japan
*These authors have contributed equally to this work
Atsushi Shiozaki, email: email@example.com
Keywords: AQP1(aquaporin 1); esophageal squamous cell carcinoma; apoptosis; death receptor signaling; cellular physiology
Received: January 22, 2018 Accepted: June 19, 2018 Published: July 06, 2018
Aquaporin 1 (AQP1) is a membrane protein whose main function is to transfer water across cellular membranes. Recent studies have described important roles for AQP1 in epithelial carcinogenesis and tumor behavior. The objectives of the present study were to investigate the role of AQP1 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 50 primary tumor samples underwent esophagectomy. AQP1 was primarily located in the cytoplasm and/or the nuclear membrane of carcinoma cells. The 5-year survival rate of patients with the “cytoplasm dominant” expression of AQP1 (47.1%) was significantly lower than other patients (83.2%). The depletion of AQP1 using siRNA induced apoptosis in TE5 and TE15 cells. The results of microarray analysis revealed that Death receptor signaling pathway-related genes were changed in AQP1-depleted TE5 cells. In conclusion, the results of the present study suggested that the cytoplasm dominant expression of AQP1 is related to a poor prognosis in patients with ESCC, and that it activates tumor progression by affecting Death receptor signaling pathway. These results provide insights into the role of AQP1 as a mediator of and/or a biomarker for ESCC.
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