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Detail of SuppFig4F_ER_ErbB2i

Yu Muta, Yoshihisa Fujita, Kenta Sumiyama, Atsuro Sakurai, M Mark Taketo, Tsutomu Chiba, Hiroshi Seno, Kazuhiro Aoki, Michiyuki Matsuda, Masamichi Imajo (2018) Composite regulation of ERK activity dynamics underlying tumour-specific traits in the intestine., Nature communications, Volume 9, Number 1, pp. 2174

Published in 2018 Jun 5 (Electronic publication in June 5, 2018, midnight )

• doi: 10.1038/s41467-018-04527-8
• pmid: 29872037
  

(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.

• Animals
• Cell Culture Techniques
• Cell Transformation, Neoplastic/genetics[major]
• Epithelial Cells/metabolism[major]
• Extracellular Signal-Regulated MAP Kinases/genetics[major]
• Extracellular Signal-Regulated MAP Kinases/metabolism
• Gene Expression Profiling[major]
• Intestines/cytology[major]
• Kinetics
• MAP Kinase Signaling System/genetics
• Mice, Inbred C57BL
• Mice, Transgenic
• Microscopy, Fluorescence, Multiphoton
• Organoids/cytology
• Organoids/metabolism
• Time-Lapse Imaging/methods