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Title: Composite regulation of ERK activity dynamics underlying tumour-specific traits in the intestine
Authors: Muta, Yu
Fujita, Yoshihisa  kyouindb  KAKEN_id
Sumiyama, Kenta
Sakurai, Atsuro
Taketo, M. Mark
Chiba, Tsutomu
Seno, Hiroshi  kyouindb  KAKEN_id
Aoki, Kazuhiro
Matsuda, Michiyuki  kyouindb  KAKEN_id  orcid (unconfirmed)
Imajo, Masamichi  kyouindb  KAKEN_id
Author's alias: 牟田, 優
藤田, 芳久
隅山, 健太
櫻井, 敦朗
武藤, 誠
千葉, 勉
妹尾, 浩
青木, 一洋
松田, 道行
今城, 正道
Keywords: Colorectal cancer
Fluorescence imaging
Growth factor signalling
Issue Date: 5-Jun-2018
Publisher: Springer Nature
Journal title: Nature communications
Volume: 9
Thesis number: 2174
Abstract: Acting downstream of many growth factors, extracellular signal-regulated kinase (ERK) plays a pivotal role in regulating cell proliferation and tumorigenesis, where its spatiotemporal dynamics, as well as its strength, determine cellular responses. Here, we uncover the ERK activity dynamics in intestinal epithelial cells (IECs) and their association with tumour characteristics. Intravital imaging identifies two distinct modes of ERK activity, sustained and pulse-like activity, in IECs. The sustained and pulse-like activities depend on ErbB2 and EGFR, respectively. Notably, activation of Wnt signalling, the earliest event in intestinal tumorigenesis, augments EGFR signalling and increases the frequency of ERK activity pulses through controlling the expression of EGFR and its regulators, rendering IECs sensitive to EGFR inhibition. Furthermore, the increased pulse frequency is correlated with increased cell proliferation. Thus, ERK activity dynamics are defined by composite inputs from EGFR and ErbB2 signalling in IECs and their alterations might underlie tumour-specific sensitivity to pharmacological EGFR inhibition.
Description: 生体内で細胞の増殖を制御する仕組みの一端を解明 --細胞増殖シグナルの可視化に成功し、腫瘍形成における変化を解明--. 京都大学プレスリリース. 2018-07-04.
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/s41467-018-04527-8
PubMed ID: 29872037
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