title: EPH-EPHRIN in human gastrointestinal cancers.
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.
authors.affiliation: 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.
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Sugimura
authors.forename: Jian-Dong
authors.initials: JD
authors.lastname: Wang
authors.forename: Hiroki
authors.initials: H
authors.lastname: Mori
authors.forename: Masaru
authors.initials: M
authors.lastname: Tsuboi
authors.forename: Kiyoko
authors.initials: K
authors.lastname: Nagura
authors.forename: Hisaki
authors.initials: H
authors.lastname: Igarashi
authors.forename: Hong
authors.initials: H
authors.lastname: Tao
authors.forename: Ritsuko
authors.initials: R
authors.lastname: Nakamura
authors.forename: Hiroko
authors.initials: H
authors.lastname: Natsume
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Kahyo
authors.forename: Kazuya
authors.initials: K
authors.lastname: Shinmura
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Konno
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Hamaya
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kanaoka
authors.forename: Hideki
authors.initials: H
authors.lastname: Kataoka
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Zhou