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Title: Cell-type dependent enhancer binding of the EWS/ATF1 fusion gene in clear cell sarcomas
Authors: Komura, Shingo
Ito, Kenji
Ohta, Sho
Ukai, Tomoyo
Kabata, Mio
Itakura, Fumiaki
Semi, Katsunori
Matsuda, Yutaka
Hashimoto, Kyoichi
Shibata, Hirofumi
Sone, Masamitsu
Jo, Norihide
Sekiguchi, Kazuya
Ohno, Takatoshi
Akiyama, Haruhiko
Shimizu, Katsuji
Woltjen, Knut
Ozawa, Manabu
Toguchida, Junya
Yamamoto, Takuya
Yamada, Yasuhiro
Author's alias: 河村, 真吾
伊藤, 謙治
太田, 翔
鵜飼, 智代
蒲田, 未央
板倉, 史晃
蝉, 克憲
松田, 穣
橋本, 恭一
柴田, 博史
曽根, 正光
城, 憲秀
大野, 貴敏
秋山, 治彦
清水, 克時
小沢, 学
戸口田, 淳也
山本, 拓也
山田, 泰広
Keywords: Cancer models
Reprogramming
Issue Date: Dec-2019
Publisher: Springer Nature
Journal title: Nature Communications
Volume: 10
Thesis number: 3999
Abstract: Clear cell sarcoma (CCS) is a rare soft tissue sarcoma caused by the EWS/ATF1 fusion gene. Here, we established induced pluripotent stem cells (iPSCs) from EWS/ATF1-controllable murine CCS cells harboring sarcoma-associated genetic abnormalities. Sarcoma-iPSC mice develop secondary sarcomas immediately after EWS/ATF1 induction, but only in soft tissue. EWS/ATF1 expression induces oncogene-induced senescence in most cell types in sarcoma-iPSC mice but prevents it in sarcoma cells. We identify Tppp3-expressing cells in peripheral nerves as a cell-of-origin for these sarcomas. We show cell type-specific recruitment of EWS/ATF1 to enhancer regions in CCS cells. Finally, epigenetic silencing at these enhancers induces senescence and inhibits CCS cell growth through altered EWS/ATF1 binding. Together, we propose that distinct responses to premature senescence are the basis for the cell type-specificity of cancer development.
Description: 細胞老化による発がん抑制作用を個体レベルで解明 --細胞老化の仕組みを利用した新たながん治療法開発に向けて--. 京都大学プレスリリース. 2019-09-11.
Rights: © The Author(s) 2019. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
URI: http://hdl.handle.net/2433/243965
DOI(Published Version): 10.1038/s41467-019-11745-1
PubMed ID: 31488818
Related Link: http://www.kyoto-u.ac.jp/ja/research/research_results/2019/190905_2.html
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