Editorial
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World J Gastrointest Oncol. Dec 15, 2010; 2(12): 421-428
Published online Dec 15, 2010. doi: 10.4251/wjgo.v2.i12.421
EPH-EPHRIN in human gastrointestinal cancers
Haruhiko Sugimura, Jian-Dong Wang, Hiroki Mori, Masaru Tsuboi, Kiyoko Nagura, Hisaki Igarashi, Hong Tao, Ritsuko Nakamura, Hiroko Natsume, Tomoaki Kahyo, Kazuya Shinmura, Hiroyuki Konno, Yasushi Hamaya, Shigeru Kanaoka, Hideki Kataoka, Xiao-Jun Zhou
Haruhiko Sugimura, Hiroki Mori, Masaru Tsuboi, Kiyoko Nagura, Hisaki Igarashi, Hong Tao, Ritsuko Nakamura, Hiroko Natsume, Tomoaki Kahyo, Kazuya Shinmura, Department of Pathology I, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan
Jian-Dong Wang, Xiao-Jun Zhou, Department of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, Jiangsu Province, China
Hiroyuki Konno, Department of Surgery II, Hamamatsu University School of Medicine, Hamamatsu, 431-3192, Japan
Yasushi Hamaya, Shigeru Kanaoka, Department of Molecular Diagnostics, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan
Hideki Kataoka, Department of Medicine I, Hamamatsu University School of Medicine, Hamamatsu, 431-3192, Japan
Author contributions: Sugimura H and Wang JD wrote the paper and the others contributed the figures, data, ideas and editing; all the authors approved the content.
Supported by A Grant in Aid for Scientific Research (2001407, 22659072, 22590356, 22790378, 221S0001) from the Ministry of Education, Culture, Sports, Science and Technology of Japan; a Grant in Aid for the 3rd anti-Cancer from the Ministry of Health, Labour and Welfare (H22-017) and from the Smoking Research Foundation
Correspondence to: Haruhiko Sugimura, MD, PhD, Department of Pathology I, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ward, Hamamatsu 431-3192, Japan. hsugimur@hama-med.ac.jp
Telephone: +81-53-4352220 Fax: +81-53-4352225
Received: August 31, 2010
Revised: December 6, 2010
Accepted: December 13, 2010
Published online: December 15, 2010
Abstract

Ever since its discovery two decades ago, the erythropoietin-producing hepatoma (EPH)-EPHRIN system has been shown to play multifaceted roles in human gastroenterological cancer as well as neurodevelopment. Over-expression, amplification and point mutations have been found in many human cancers and many investigators have shown correlations between these up-regulations and tumor angiogenesis. Thus, the genes in this family are considered to be potential targets of cancer therapy. On the other hand, the down-regulation of some members as a result of epigenetic changes has also been reported in some cancers. Furthermore, the correlation between altered expressions and clinical prognosis seems to be inconclusive. A huge amount of protein-protein interaction studies on the EPH-EPHRIN system have provided a basic scheme for signal transductions, especially bi-directional signaling involving EPH-ERPHRIN molecules at the cell membrane. This information also provides a manipulative strategy for harnessing the actions of these molecules. In this review, we summarize the known alterations of EPH-EPHRIN genes in human tumors of the esophagus, stomach, colorectum, liver and pancreas and present the perspective that the EPH-EPHRIN system could be a potential target of cancer therapy.

Keywords: Erythropoietin-producing hepatoma; EPH-EPHRIN; Gastric cancer; Colorectal cancer; Methylation; Secreted form