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

Kon, Shunsuke; Ishibashi, Kojiro; Katoh, Hiroto et al.

Nature Cell Biology, 2017, 19(5), 530-541

Permalink : https://hdl.handle.net/2115/67502

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論文情報

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アクセス権
open access
URI
https://hdl.handle.net/2115/67502
タイトル
Cell competition with normal epithelial cells promotes apical extrusion of transformed cells through metabolic changes
著者
Kon, Shunsuke ; Ishibashi, Kojiro ; Katoh, Hiroto ; Kitamoto, Sho ; Shirai, Takanobu ; Tanaka, Shinya ; Kajita, Mihoko ; Ishikawa, Susumu ; Yamauchi, Hajime ; Yako, Yuta ; Kamasaki, Tomoko ; Matsumoto, Tomohiro ; Watanabe, Hirotaka ; Egami, Riku ; Sasaki, Ayana ; Nishikawa, Atsuko ; Kameda, Ikumi ; Maruyama, Takeshi ; Narumi, Rika ; Morita, Tomoko ; Sasaki, Yoshiteru ; Enoki, Ryosuke ; Honma, Sato ; Imamura, Hiromi ; Oshima, Masanobu ; Soga, Tomoyoshi ; Miyazaki, Jun-ichi ; Duchen, Michael R. ; Nam, Jin-Min ; Onodera, Yasuhito ; Yoshioka, Shingo ; Kikuta, Junichi ; Ishii, Masaru ; Imajo, Masamichi ; Nishida, Eisuke ; Fujioka, Yoichiro ; Ohba, Yusuke ; Sato, Toshiro ; Fujita, Yasuyuki
e-Rad_Researcher
70506641
著者名
Kon, Shunsuke
著者名
Ishibashi, Kojiro
著者名
Katoh, Hiroto
著者名
Kitamoto, Sho
著者名
Shirai, Takanobu
著者名
Tanaka, Shinya
e-Rad_Researcher
00607442
著者名
Kajita, Mihoko
著者名
Ishikawa, Susumu
著者名
Yamauchi, Hajime
著者名
Yako, Yuta
著者名
Kamasaki, Tomoko
著者名
Matsumoto, Tomohiro
著者名
Watanabe, Hirotaka
著者名
Egami, Riku
著者名
Sasaki, Ayana
著者名
Nishikawa, Atsuko
著者名
Kameda, Ikumi
著者名
Maruyama, Takeshi
著者名
Narumi, Rika
著者名
Morita, Tomoko
著者名
Sasaki, Yoshiteru
e-Rad_Researcher
00528341
著者名
Enoki, Ryosuke
e-Rad_Researcher
20142713
著者名
Honma, Sato
著者名
Imamura, Hiromi
著者名
Oshima, Masanobu
著者名
Soga, Tomoyoshi
著者名
Miyazaki, Jun-ichi
著者名
Duchen, Michael R.
著者名
Nam, Jin-Min
e-Rad_Researcher
90435561
著者名
Onodera, Yasuhito
著者名
Yoshioka, Shingo
著者名
Kikuta, Junichi
e-Rad_Researcher
10324758
著者名
Ishii, Masaru
著者名
Imajo, Masamichi
著者名
Nishida, Eisuke
著者名
Fujioka, Yoichiro
e-Rad_Researcher
30333503
著者名
Ohba, Yusuke
著者名
Sato, Toshiro
e-Rad_Researcher
50580974
著者名
Fujita, Yasuyuki
言語
英語
発行日
2017-05
出版者
Nature Publishing Group
収録物名
Nature Cell Biology
巻(号)
19(5)
ページ
530-541
抄録
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.
資源タイプ
学術雑誌論文
出版タイプ
Accepted Manuscript
PISSN
1465-7392
EISSN
1476-4679
関連情報
PMID
28414314
関連情報 (isVersionOf)
出版社版DOI
https://doi.org/10.1038/ncb3509