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

Muta, Yu  ,  Fujita, Yoshihisa  ,  Sumiyama, Kenta  ,  Sakurai, Atsuro  ,  Taketo, M. Mark  ,  Chiba, Tsutomu  ,  Seno, Hiroshi  ,  Aoki, Kazuhiro  ,  Matsuda, Michiyuki  ,  Imajo, Masamichi

92018-06-05 , Springer Nature
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.
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.

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