論文 - 詳細
| RRC ID | 47662 |
|---|---|
| 著者 | Vaughen J, Igaki T. |
| タイトル | Slit-Robo Repulsive Signaling Extrudes Tumorigenic Cells from Epithelia. |
| ジャーナル | Dev Cell |
| Abstract |
Cells dynamically interact throughout animal development to coordinate growth and deter disease. For example, cell-cell competition weeds out aberrant cells to enforce homeostasis. In Drosophila, tumorigenic cells mutant for the cell polarity gene scribble (scrib) are actively eliminated from epithelia when surrounded by wild-type cells. While scrib cell elimination depends critically on JNK signaling, JNK-dependent cell death cannot sufficiently explain scrib cell extirpation. Thus, how JNK executed cell elimination remained elusive. Here, we show that repulsive Slit-Robo2-Ena signaling exerts an extrusive force downstream of JNK to eliminate scrib cells from epithelia by disrupting E-cadherin. While loss of Slit-Robo2-Ena in scrib cells potentiates scrib tumor formation within the epithelium, Robo2-Ena hyperactivation surprisingly triggers luminal scrib tumor growth following excess extrusion. This extrusive signaling is amplified by a positive feedback loop between Slit-Robo2-Ena and JNK. Our observations provide a potential causal mechanism for Slit-Robo dysregulation in numerous human cancers. |
| 巻・号 | 39(6) |
| ページ | 683-695 |
| 公開日 | 2016-12-19 |
| DOI | 10.1016/j.devcel.2016.11.015 |
| PII | S1534-5807(16)30827-9 |
| PMID | 27997825 |
| PMC | PMC6207184 |
| MeSH | Animals Cadherins / metabolism Carcinogenesis / metabolism Carcinogenesis / pathology Clone Cells Drosophila Proteins / metabolism* Drosophila melanogaster / metabolism* Epithelium / metabolism* Epithelium / pathology* Feedback, Physiological JNK Mitogen-Activated Protein Kinases / metabolism Models, Biological Neoplasms / metabolism* Neoplasms / pathology* Nerve Tissue Proteins / metabolism* Receptors, Immunologic / metabolism* Signal Transduction* Up-Regulation |
| IF | 10.092 |
| 引用数 | 37 |
| WOS 分野 | DEVELOPMENTAL BIOLOGY CELL BIOLOGY |
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 12 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
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