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Title: In vivo reprogramming drives Kras-induced cancer development
Authors: Shibata, Hirofumi
Komura, Shingo
Yamada, Yosuke  kyouindb  KAKEN_id
Sankoda, Nao
Tanaka, Akito
Ukai, Tomoyo
Kabata, Mio
Sakurai, Satoko
Kuze, Bunya
Woltjen, Knut  kyouindb  KAKEN_id  orcid (unconfirmed)
Haga, Hironori  kyouindb  KAKEN_id
Ito, Yatsuji
Kawaguchi, Yoshiya  kyouindb  KAKEN_id
Yamamoto, Takuya  kyouindb  KAKEN_id
Yamada, Yasuhiro
Author's alias: 柴田, 博史
河村, 真吾
山田, 洋介
三小田, 直
鵜飼, 智代
蒲田, 未央
櫻井, 智子
久世, 文也
ウォルツェン, クヌート
羽賀, 博典
伊藤, 八次
川口, 義弥
山本, 拓也
山田, 泰広
Keywords: Cancer models
Induced pluripotent stem cells
Issue Date: 25-May-2018
Publisher: Springer Nature
Journal title: Nature Communications
Volume: 9
Thesis number: 2081
Abstract: The faithful shutdown of the somatic program occurs in the early stage of reprogramming. Here, we examined the effect of in vivo reprogramming on Kras-induced cancer development. We show that the transient expression of reprogramming factors (1–3 days) in pancreatic acinar cells results in the transient repression of acinar cell enhancers, which are similarly observed in pancreatitis. We next demonstrate that Kras and p53 mutations are insufficient to induce ERK signaling in the pancreas. Notably, the transient expression of reprogramming factors in Kras mutant mice is sufficient to induce the robust and persistent activation of ERK signaling in acinar cells and rapid formation of pancreatic ductal adenocarcinoma. In contrast, the forced expression of acinar cell-related transcription factors inhibits the pancreatitis-induced activation of ERK signaling and development of precancerous lesions in Kras-mutated acinar cells. These results underscore a crucial role of dedifferentiation-associated epigenetic regulations in the initiation of pancreatic cancers.
Description: 膵臓がんが発生する新たなメカニズムを解明 --遺伝子変異とは異なるがんの原因--. 京都大学プレスリリース. 2018-06-01.
Rights: © The Author(s) 2018. 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
DOI(Published Version): 10.1038/s41467-018-04449-5
PubMed ID: 29802314
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