論文 - 詳細
| RRC ID | 53828 |
|---|---|
| 著者 | Muta Y, Fujita Y, Sumiyama K, Sakurai A, Taketo MM, Chiba T, Seno H, Aoki K, Matsuda M, Imajo M. |
| タイトル | Composite regulation of ERK activity dynamics underlying tumour-specific traits in the intestine. |
| ジャーナル | Nat Commun |
| 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. |
| 巻・号 | 9(1) |
| ページ | 2174 |
| 公開日 | 2018-6-5 |
| DOI | 10.1038/s41467-018-04527-8 |
| PII | 10.1038/s41467-018-04527-8 |
| PMID | 29872037 |
| PMC | PMC5988836 |
| MeSH | Animals Cell Culture Techniques Cell Transformation, Neoplastic / genetics* Epithelial Cells / metabolism* Extracellular Signal-Regulated MAP Kinases / genetics* Extracellular Signal-Regulated MAP Kinases / metabolism Gene Expression Profiling* Intestines / cytology* Kinetics MAP Kinase Signaling System / genetics Mice, Inbred C57BL Mice, Transgenic Microscopy, Fluorescence, Multiphoton Organoids / cytology Organoids / metabolism Time-Lapse Imaging / methods |
| IF | 12.121 |
| 引用数 | 12 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 5 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 遺伝子材料 | pCMV-VSV-G-RSV-Rev (RDB04393) |
| 実験動物マウス | RBRC06511 |