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Rab5-regulated endocytosis plays a crucial role in apical extrusion of transformed cells

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タイトル: Rab5-regulated endocytosis plays a crucial role in apical extrusion of transformed cells
著者: Saitoh, Sayaka 著作を一覧する
Maruyama, Takeshi 著作を一覧する
Yako, Yuta 著作を一覧する
Kajita, Mihoko 著作を一覧する
Fujioka, Yoichiro 著作を一覧する
Ohba, Yusuke 著作を一覧する
Kasai, Nobuhiro 著作を一覧する
Sugama, Natsu 著作を一覧する
Kon, Shunsuke 著作を一覧する
Ishikawa, Susumu 著作を一覧する
Hayashi, Takashi 著作を一覧する
Yamazaki, Tomohiro 著作を一覧する
Tada, Masazumi 著作を一覧する
Fujita, Yasuyuki 著作を一覧する
キーワード: cell competition
endocytosis
apical extrusion
Rab5
RasV12
発行日: 2017年 3月21日
出版者: National Academy of Sciences
誌名: Proceedings of the National Academy of Sciences of the United States of America
巻: 114
号: 12
開始ページ: E2327
終了ページ: E2336
出版社 DOI: 10.1073/pnas.1602349114
抄録: Newly emerging transformed cells are often eliminated from epithelial tissues. Recent studies have revealed that this cancer-preventive process involves the interaction with the surrounding normal epithelial cells; however, the molecular mechanisms underlying this phenomenon remain largely unknown. In this study, using mammalian cell culture and zebrafish embryo systems, we have elucidated the functional involvement of endocytosis in the elimination of RasV12-transformed cells. First, we show that Rab5, a crucial regulator of endocytosis, is accumulated in RasV12-transformed cells that are surrounded by normal epithelial cells, which is accompanied by up-regulation of clathrin-dependent endocytosis. Addition of chlorpromazine or coexpression of a dominant-negative mutant of Rab5 suppresses apical extrusion of RasV12 cells from the epithelium. We also show in zebrafish embryos that Rab5 plays an important role in the elimination of transformed cells from the enveloping layer epithelium. In addition, Rab5-mediated endocytosis of E-cadherin is enhanced at the boundary between normal and RasV12 cells. Rab5 functions upstream of epithelial protein lost in neoplasm (EPLIN), which plays a positive role in apical extrusion of RasV12 cells by regulating protein kinase A. Furthermore, we have revealed that epithelial defense against cancer (EDAC) from normal epithelial cells substantially impacts on Rab5 accumulation in the neighboring transformed cells. This report demonstrates that Rab5-mediated endocytosis is a crucial regulator for the competitive interaction between normal and transformed epithelial cells in mammals.
資料タイプ: article (author version)
URI: http://hdl.handle.net/2115/67160
出現コレクション:雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

提供者: 藤田 恭之

 

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