Title: | Cell competition with normal epithelial cells promotes apical extrusion of transformed cells through metabolic changes |
Authors: | Kon, Shunsuke Browse this author →KAKEN DB |
Ishibashi, Kojiro Browse this author |
Katoh, Hiroto Browse this author |
Kitamoto, Sho Browse this author |
Shirai, Takanobu Browse this author |
Tanaka, Shinya Browse this author |
Kajita, Mihoko Browse this author →KAKEN DB |
Ishikawa, Susumu Browse this author |
Yamauchi, Hajime Browse this author |
Yako, Yuta Browse this author |
Kamasaki, Tomoko Browse this author |
Matsumoto, Tomohiro Browse this author |
Watanabe, Hirotaka Browse this author |
Egami, Riku Browse this author |
Sasaki, Ayana Browse this author |
Nishikawa, Atsuko Browse this author |
Kameda, Ikumi Browse this author |
Maruyama, Takeshi Browse this author |
Narumi, Rika Browse this author |
Morita, Tomoko Browse this author |
Sasaki, Yoshiteru Browse this author |
Enoki, Ryosuke Browse this author →KAKEN DB |
Honma, Sato Browse this author →KAKEN DB |
Imamura, Hiromi Browse this author |
Oshima, Masanobu Browse this author |
Soga, Tomoyoshi Browse this author |
Miyazaki, Jun-ichi Browse this author |
Duchen, Michael R. Browse this author |
Nam, Jin-Min Browse this author |
Onodera, Yasuhito Browse this author →KAKEN DB |
Yoshioka, Shingo Browse this author |
Kikuta, Junichi Browse this author |
Ishii, Masaru Browse this author →KAKEN DB |
Imajo, Masamichi Browse this author |
Nishida, Eisuke Browse this author |
Fujioka, Yoichiro Browse this author |
Ohba, Yusuke Browse this author →KAKEN DB |
Sato, Toshiro Browse this author |
Fujita, Yasuyuki Browse this author →KAKEN DB |
Issue Date: | May-2017 |
Publisher: | Nature Publishing Group |
Journal Title: | Nature Cell Biology |
Volume: | 19 |
Issue: | 5 |
Start Page: | 530 |
End Page: | 541 |
Publisher DOI: | 10.1038/ncb3509 |
PMID: | 28414314 |
Abstract: | Recent studies have revealed that newly emerging transformed cells are often apically extruded from epithelial tissues. During this process, normal epithelial cells can recognize and actively eliminate transformed cells, a process called epithelial defence against cancer (EDAC). Here, we show that mitochondrial membrane potential is diminished in RasV12-transformed cells when they are surrounded by normal cells. In addition, glucose uptake is elevated, leading to higher lactate production. The mitochondrial dysfunction is driven by upregulation of pyruvate dehydrogenase kinase 4 (PDK4), which positively regulates elimination of RasV12-transformed cells. Furthermore, EDAC from the surrounding normal cells, involving filamin, drives the Warburg-effect-like metabolic alteration. Moreover, using a cell-competition mouse model, we demonstrate that PDK-mediated metabolic changes promote the elimination of RasV12-transformed cells from intestinal epithelia. These data indicate that non-cell-autonomous metabolic modulation is a crucial regulator for cell competition, shedding light on the unexplored events at the initial stage of carcinogenesis. |
Type: | article (author version) |
URI: | http://hdl.handle.net/2115/67502 |
Appears in Collections: | 遺伝子病制御研究所 (Institute for Genetic Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc) 国際連携研究教育局 : GI-CoRE (Global Institution for Collaborative Research and Education : GI-CoRE) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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