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Cell competition with normal epithelial cells promotes apical extrusion of transformed cells through metabolic changes

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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)
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)

Submitter: 藤田 恭之

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