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タイトル: Integrated Molecular Profiling of Human Gastric Cancer Identifies DDR2 as a Potential Regulator of Peritoneal Dissemination
著者: Kurashige, Junji
Hasegawa, Takanori
Niida, Atsushi
Sugimachi, Keishi
Deng, Niantao
Mima, Kosuke
Uchi, Ryutaro
Sawada, Genta
Takahashi, Yusuke
Eguchi, Hidetoshi
Inomata, Masashi
Kitano, Seigo
Fukagawa, Takeo
Sasako, Mitsuru
Sasaki, Hiroki
Sasaki, Shin
Mori, Masaki
Yanagihara, Kazuyoshi
Baba, Hideo
Miyano, Satoru
Tan, Patrick
Mimori, Koshi
著者名の別形: 長谷川, 嵩矩
発行日: 3-Mar-2016
出版者: Nature Publishing Group
誌名: Scientific Reports
巻: 6
論文番号: 22371
抄録: Peritoneal dissemination is the most frequent, incurable metastasis occurring in patients with advanced gastric cancer (GC). However, molecular mechanisms driving peritoneal dissemination still remain poorly understood. Here, we aimed to provide novel insights into the molecular mechanisms that drive the peritoneal dissemination of GC. We performed combined expression analysis with in vivo-selected metastatic cell lines and samples from 200 GC patients to identify driver genes of peritoneal dissemination. The driver-gene functions associated with GC dissemination were examined using a mouse xenograft model. We identified a peritoneal dissemination-associated expression signature, whose profile correlated with those of genes related to development, focal adhesion, and the extracellular matrix. Among the genes comprising the expression signature, we identified that discoidin-domain receptor 2 (DDR2) as a potential regulator of peritoneal dissemination. The DDR2 was upregulated by the loss of DNA methylation and that DDR2 knockdown reduced peritoneal metastasis in a xenograft model. Dasatinib, an inhibitor of the DDR2 signaling pathway, effectively suppressed peritoneal dissemination. DDR2 was identified as a driver gene for GC dissemination from the combined expression signature and can potentially serve as a novel therapeutic target for inhibiting GC peritoneal dissemination.
著作権等: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material.
URI: http://hdl.handle.net/2433/227469
DOI(出版社版): 10.1038/srep22371
出現コレクション:学術雑誌掲載論文等

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