果蝇先天免疫系统的激活与致癌Ras协同加速生长。

IF 9.8 1区 生物学 Q1 Agricultural and Biological Sciences
PLoS Biology Pub Date : 2025-04-28 eCollection Date: 2025-04-01 DOI:10.1371/journal.pbio.3003068
Fabienne Brutscher, Federico Germani, George Hausmann, Lena Jutz, Konrad Basler
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引用次数: 0

摘要

果蝇的先天免疫作为外部刺激或细胞适应性的有机体监视系统,并触发特定环境的反应来对抗感染和维持组织稳态。然而,先天免疫途径不受控制的激活可能是有害的。在哺乳动物中,先天免疫信号通常在恶性细胞中过度激活,并有助于肿瘤的进展。果蝇肿瘤模型有助于发现促进肿瘤发生的途径之间的相互作用,但对于Toll先天免疫途径是否以及如何与癌基因相互作用知之甚少。在这里,我们使用果蝇上皮在体内模型来研究Toll信号和致癌Ras之间的相互作用。在缺乏致癌Ras (RasV12)的情况下,Toll信号传导抑制分化并诱导细胞凋亡。相反,在RasV12的情况下,细胞免于死亡,Dorsal促进细胞存活和增殖以驱动增生。综上所述,我们表明先天免疫活性的组织保护功能可以被恶性前细胞劫持,从而诱导肿瘤过度生长。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Activation of the Drosophila innate immune system accelerates growth in cooperation with oncogenic Ras.

Innate immunity in Drosophila acts as an organismal surveillance system for external stimuli or cellular fitness and triggers context-specific responses to fight infections and maintain tissue homeostasis. However, uncontrolled activation of innate immune pathways can be detrimental. In mammals, innate immune signaling is often overactivated in malignant cells and contributes to tumor progression. Drosophila tumor models have been instrumental in the discovery of interactions between pathways that promote tumorigenesis, but little is known about whether and how the Toll innate immune pathway interacts with oncogenes. Here we use a Drosophila epithelial in vivo model to investigate the interplay between Toll signaling and oncogenic Ras. In the absence of oncogenic Ras (RasV12), Toll signaling suppresses differentiation and induces apoptosis. In contrast, in the context of RasV12, cells are protected from cell death and Dorsal promotes cell survival and proliferation to drive hyperplasia. Taken together, we show that the tissue-protective functions of innate immune activity can be hijacked by pre-malignant cells to induce tumorous overgrowth.

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来源期刊
PLoS Biology
PLoS Biology BIOCHEMISTRY & MOLECULAR BIOLOGY-BIOLOGY
CiteScore
15.40
自引率
2.00%
发文量
359
审稿时长
3-8 weeks
期刊介绍: PLOS Biology is the flagship journal of the Public Library of Science (PLOS) and focuses on publishing groundbreaking and relevant research in all areas of biological science. The journal features works at various scales, ranging from molecules to ecosystems, and also encourages interdisciplinary studies. PLOS Biology publishes articles that demonstrate exceptional significance, originality, and relevance, with a high standard of scientific rigor in methodology, reporting, and conclusions. The journal aims to advance science and serve the research community by transforming research communication to align with the research process. It offers evolving article types and policies that empower authors to share the complete story behind their scientific findings with a diverse global audience of researchers, educators, policymakers, patient advocacy groups, and the general public. PLOS Biology, along with other PLOS journals, is widely indexed by major services such as Crossref, Dimensions, DOAJ, Google Scholar, PubMed, PubMed Central, Scopus, and Web of Science. Additionally, PLOS Biology is indexed by various other services including AGRICOLA, Biological Abstracts, BIOSYS Previews, CABI CAB Abstracts, CABI Global Health, CAPES, CAS, CNKI, Embase, Journal Guide, MEDLINE, and Zoological Record, ensuring that the research content is easily accessible and discoverable by a wide range of audiences.
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