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ID 112460
著者
宮脇, 慎吾 Hokkaido University|Keio University
Kawamura, Yoshimi Hokkaido University
Oiwa, Yuki Hokkaido University
Shimizu, Atsushi Iwate Medical University
Hachiya, Tsuyoshi Iwate Medical University
Bono, Hidemasa Research Organization of Information and Systems
Koya, Ikuko Keio University
Okada, Yohei Keio University|Aichi Medical University
Kimura, Tokuhiro Yamaguchi University
Tsuchiya, Yoshihiro Hoshi University
Suzuki, Sadafumi Keio University
Onishi, Nobuyuki Keio University
Kuzumaki, Naoko Keio University|Hoshi University
Matsuzaki, Yumi Shimane University
Narita, Minoru Hoshi University
Ikeda, Eiji Yamaguchi University
Okanoya, Kazuo The University of Tokyo
Seino, Ken-ichiro Hokkaido University
Saya, Hideyuki Keio University
Okano, Hideyuki Keio University
Miura, Kyoko Hokkaido University|Keio University|Japan Science and Technology Agency
資料タイプ
学術雑誌論文
抄録
The naked mole-rat (NMR, Heterocephalus glaber), which is the longest-lived rodent species, exhibits extraordinary resistance to cancer. Here we report that NMR somatic cells exhibit a unique tumour-suppressor response to reprogramming induction. In this study, we generate NMR-induced pluripotent stem cells (NMR-iPSCs) and find that NMR-iPSCs do not exhibit teratoma-forming tumorigenicity due to the species-specific activation of tumour-suppressor alternative reading frame (ARF) and a disruption mutation of the oncogene ES cell-expressed Ras (ERAS). The forced expression of Arf in mouse iPSCs markedly reduces tumorigenicity. Furthermore, we identify an NMR-specific tumour-suppression phenotype—ARF suppression-induced senescence (ASIS)—that may protect iPSCs and somatic cells from ARF suppression and, as a consequence, tumorigenicity. Thus, NMR-specific ARF regulation and the disruption of ERAS regulate tumour resistance in NMR-iPSCs. Our findings obtained from studies of NMR-iPSCs provide new insight into the mechanisms of tumorigenicity in iPSCs and cancer resistance in the NMR.
掲載誌名
Nature Communications
ISSN
20411723
cat書誌ID
AA12645905
出版者
Springer Nature
7
開始ページ
11471
発行日
2016-05-10
備考
Supplementary Information : ncomms_7_11471_s1.pdf
権利情報
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. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
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出版社版DOI
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言語
eng
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部局
先端酵素学研究所