Composite regulation of ERK activity dynamics underlying tumour-specific traits in the intestine

Yu Muta, Yoshihisa Fujita, Kenta Sumiyama, Atsuro Sakurai, M. Mark Taketo, Tsutomu Chiba, Hiroshi Seno, Kazuhiro Aoki, Michiyuki Matsuda and Masamichi Imajo ()
Additional contact information
Yu Muta: Kyoto University
Yoshihisa Fujita: Kyoto University
Kenta Sumiyama: Laboratory for Mouse Genetic Engineering, Quantitative Biology Center, RIKEN
Atsuro Sakurai: Laboratory of Bioimaging and Cell Signaling, Graduate School of Biostudies, Kyoto University
M. Mark Taketo: Division of Experimental Therapeutics, Graduate School of Medicine, Kyoto University
Tsutomu Chiba: Kyoto University
Hiroshi Seno: Kyoto University
Kazuhiro Aoki: Okazaki Institute for Integrative Bioscience, National Institute for Basic Biology, National Institutes of Natural Sciences
Michiyuki Matsuda: Kyoto University
Masamichi Imajo: Laboratory of Bioimaging and Cell Signaling, Graduate School of Biostudies, Kyoto University

Nature Communications, 2018, vol. 9, issue 1, 1-16

Abstract: 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.

Date: 2018
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-018-04527-8 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-04527-8

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-018-04527-8

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().