論文 - 詳細
| RRC ID | 70358 |
|---|---|
| 著者 | Ding X, Li Z, Lin G, Li W, Xue L. |
| タイトル | Toll-7 promotes tumour growth and invasion in Drosophila. |
| ジャーナル | Cell Prolif |
| Abstract |
OBJECTIVES:Drosophila melanogaster has become an excellent model organism to explore the genetic mechanisms underlying tumour progression. Here, by using well-established Drosophila tumour models, we identified Toll-7 as a novel regulator of tumour growth and invasion. MATERIALS AND METHODS:Transgenic flies and genetic epistasis analysis were used. All flies were raised on a standard cornmeal and agar medium at 25°C unless otherwise indicated. Immunostaining and RT-qPCR were performed by standard procedures. Images were taken by OLYMPUS BX51 microscope and Zeiss LSM 880 confocal microscope. Adobe Photoshop 2020 and Zeiss Zen were used to analyse the images. All results were presented in Scatter plots or Column bar graphs created by GraphPad Prism 8.0. RESULTS:Loss of Toll-7 suppresses RasV12 /lgl-/- -induced tumour growth and invasion, as well as cell polarity disruption-induced invasive cell migration, whereas expression of a constitutively active allele of Toll-7 is sufficient to promote tumorous growth and cell migration. In addition, the Egr-JNK signalling is necessary and sufficient for Toll-7-induced invasive cell migration. Mechanistically, Toll-7 facilitates the endocytosis of Egr, which is known to activate JNK in the early endosomes. Moreover, Toll-7 activates the EGFR-Ras signalling, which cooperates with the Egr-JNK signalling to promote Yki-mediated cell proliferation and tissue overgrowth. Finally, Toll-7 is necessary and sufficient for the proper maintenance of EGFR protein level. CONCLUSIONS:Our findings characterized Toll-7 as a proto-oncogene that promotes tumour growth and invasion in Drosophila, which shed light on the pro-tumour function of mammalian Toll-like receptors (TLRs). |
| 巻・号 | 55(2) |
| ページ | e13188 |
| 公開日 | 2022-2-1 |
| DOI | 10.1111/cpr.13188 |
| PMID | 35050535 |
| PMC | PMC8828261 |
| MeSH | Animals Animals, Genetically Modified Cell Movement / physiology* Cell Polarity / physiology* Cell Proliferation / genetics* Drosophila / metabolism Drosophila Proteins / metabolism Drosophila melanogaster / genetics JNK Mitogen-Activated Protein Kinases / metabolism MAP Kinase Signaling System / genetics* Neoplasms / pathology* Signal Transduction / genetics |
| IF | 5.753 |
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| ショウジョウバエ | |