摘要
Ever since its discovery two decades ago,the erythro- poietin-producing hepatoma (EPH)-EPHRIN system has been shown to play multifaceted roles in human gastroenterological cancer as well as neurodevelopment.Overexpression,amplif ication and point mutations have been found in many human cancers and many investigators have shown correlations between these up-regulationsand 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.
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.
基金
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
