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Abstract
The extracellular signal-regulated kinase (ERK) signaling pathway regulates a variety of biological processes including cell proliferation, survival, and differentiation. Since ERK activation promotes proliferation of many types of cells, its deregulated/constitutive activation is among general mechanisms for cancer. Recent advances in bioimaging techniques have enabled to visualize ERK activity in real-time at the single-cell level. Emerging evidence from such approaches suggests unexpectedly complex spatiotemporal dynamics of ERK activity in living cells and animals and their crucial roles in determining cellular responses. In this review, we discuss how ERK activity dynamics are regulated and how they affect biological processes including cell fate decisions, cell migration, embryonic development, tissue homeostasis, and tumorigenesis.
Highlights
The extracellular signal-regulated kinase (ERK) pathway is an evolutionarily conserved signaling pathway that regulates a variety of cellular processes including cell survival, proliferation, and differentiation [1,2,3,4]
In spite of the apparent significance of the in many cancers, it remains elusive how ERK activity dynamics are altered at the single cell level and pathway in many cancers, it remains elusive how ERK activity dynamics are altered at the single cell how it affects cellular functions during oncogenesis
Intestinal epithelial cells (IECs) highly dependent on EGF receptor (EGFR) signaling [35]. These findings provide a therapeutic rationale for why EGFR inhibitors can target colorectal cancers (CRCs) in clinical practice without causing severe damage to the normal tissues (Figure 2)
Summary
The extracellular signal-regulated kinase (ERK) pathway is an evolutionarily conserved signaling pathway that regulates a variety of cellular processes including cell survival, proliferation, and differentiation [1,2,3,4]. In order to fulfill specific function, ERK activity is strictly regulated by many mechanisms depending on the cellular context (Figure 1). The ERK pathway is regulated by multiple feedback loops at different levels of the signaling cascade [5,6], which defines temporal dynamics of ERK activity. In spite of the apparent significance of the in many cancers, it remains elusive how ERK activity dynamics are altered at the single cell level and pathway in many cancers, it remains elusive how ERK activity dynamics are altered at the single cell how it affects cellular functions during oncogenesis. We will focus on physiological significance of ERK activity dynamics in several biological contexts, especially focusing on intestinal tumorigenesis
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