Toll-7 promotes tumour growth and invasion in Drosophila.
Toll-7 promotes tumour growth and invasion in Drosophila.
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DOI：
10.1111/cpr.13188
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发表时间：
2022-03
影响因子：
8.5
通讯作者：
Xue L
中科院分区：
文献类型：
--
作者：
Ding X;Li Z;Lin G;Li W;Xue L
黑腹果蝇已成为探索肿瘤进展遗传机制的优秀模型生物。在这里，通过使用完善的果蝇肿瘤模型，我们确定 Toll-7 是肿瘤生长和侵袭的新型调节剂。使用转基因果蝇和遗传上位分析。除非另有说明，所有果蝇均在 25°C 的标准玉米粉和琼脂培养基上饲养。免疫染色和 RT-qPCR 按标准程序进行。图像由 OLYMPUS BX51 显微镜和 Zeiss LSM 880 共焦显微镜拍摄。使用 Adobe Photoshop 2020 和 Zeiss Zen 来分析图像。所有结果均以 GraphPad Prism 8.0 创建的散点图或柱形图形式呈现。 Toll-7 的缺失会抑制 RasV12/lgl -/- 诱导的肿瘤生长和侵袭，以及细胞极性破坏诱导的侵袭性细胞迁移，而 Toll-7 的组成型活性等位基因的表达足以促进肿瘤生长和细胞迁移。此外，Egr-JNK 信号传导对于 Toll-7 诱导的侵袭性细胞迁移是必要且充分的。从机制上讲，Toll-7 促进 Egr 的内吞作用，已知 Egr 可以激活早期内体中的 JNK。此外，Toll-7 激活 EGFR-Ras 信号传导，该信号传导与 Egr-JNK 信号传导协同促进 Yki 介导的细胞增殖和组织过度生长。最后，Toll-7 对于适当维持 EGFR 蛋白水平是必要且充分的。我们的研究结果将 Toll-7 描述为一种原癌基因，可促进果蝇肿瘤的生长和侵袭，这揭示了哺乳动物 Toll 样受体 (TLR) 的促肿瘤功能。在这项研究中，我们将 Toll-7 确定为一种原癌基因，通过 Egr-JNK 和 EGFR-Ras 信号传导促进肿瘤生长和侵袭。从机制上讲，Toll-7 促进 Egr 的内吞作用，已知 Egr 可以激活早期内体中的 JNK。 Toll-7 促进 EGFR 转录后表达，从而激活 ERK。我们的结果为 Toll-7 在促进肿瘤发生中的作用提供了体内证据和潜在的遗传机制。
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. 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. 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. 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). In this study, we identified Toll‐7 as a proto‐oncogene that promotes tumour growth and invasion through Egr‐JNK and EGFR‐Ras signalling. Mechanistically, Toll‐7 facilitates the endocytosis of Egr, which is known to activate JNK in the early endosomes. Toll‐7 promotes EGFR expression post‐transcriptionally to activate ERK. Our results provide in‐vivo evidence and underlying genetic mechanism for the role of Toll‐7 in promoting tumorigenesis.
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影响因子：
7.7
作者：
Bunker BD;Nellimoottil TT;Boileau RM;Classen AK;Bilder D
通讯作者：
Bilder D
影响因子：
7.3
作者：
Amoyel M;Anderson AM;Bach EA
通讯作者：
Bach EA
DOI：
10.1073/pnas.1113882109
发表时间：
2012-01-10
影响因子：
11.1
作者：
Chen, Chiao-Lin;Schroeder, Molly C.;Halder, Georg
通讯作者：
Halder, Georg
影响因子：
--
作者：
Doggett K;Grusche FA;Richardson HE;Brumby AM
通讯作者：
Brumby AM
影响因子：
11.2
作者：
Huang, B;Zhao, J;Xiong, HB
通讯作者：
Xiong, HB