دورية أكاديمية
Netrin signaling mediates survival of dormant epithelial ovarian cancer cells
| العنوان: | Netrin signaling mediates survival of dormant epithelial ovarian cancer cells |
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| المؤلفون: | Pirunthan Perampalam, James I MacDonald, Komila Zakirova, Daniel T Passos, Sumaiyah Wasif, Yudith Ramos-Valdes, Maeva Hervieu, Patrick Mehlen, Rob Rottapel, Benjamin Gibert, Rohann JM Correa, Trevor G Shepherd, Frederick A Dick |
| المصدر: | eLife, Vol 12 (2024) |
| بيانات النشر: | eLife Sciences Publications Ltd, 2024. |
| سنة النشر: | 2024 |
| المجموعة: | LCC:Medicine LCC:Science LCC:Biology (General) |
| مصطلحات موضوعية: | Netrin, high grade serous ovarian cancer, Dyrk1a, dormancy, quiescence, spheroids, Medicine, Science, Biology (General), QH301-705.5 |
| الوصف: | Dormancy in cancer is a clinical state in which residual disease remains undetectable for a prolonged duration. At a cellular level, rare cancer cells cease proliferation and survive chemotherapy and disseminate disease. We created a suspension culture model of high-grade serous ovarian cancer (HGSOC) dormancy and devised a novel CRISPR screening approach to identify survival genes in this context. In combination with RNA-seq, we discovered the Netrin signaling pathway as critical to dormant HGSOC cell survival. We demonstrate that Netrin-1, –3, and its receptors are essential for low level ERK activation to promote survival, and that Netrin activation of ERK is unable to induce proliferation. Deletion of all UNC5 family receptors blocks Netrin signaling in HGSOC cells and compromises viability during the dormancy step of dissemination in xenograft assays. Furthermore, we demonstrate that Netrin-1 and –3 overexpression in HGSOC correlates with poor outcome. Specifically, our experiments reveal that Netrin overexpression elevates cell survival in dormant culture conditions and contributes to greater spread of disease in a xenograft model of abdominal dissemination. This study highlights Netrin signaling as a key mediator HGSOC cancer cell dormancy and metastasis. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2050-084X |
| Relation: | https://elifesciences.org/articles/91766; https://doaj.org/toc/2050-084X |
| DOI: | 10.7554/eLife.91766 |
| URL الوصول: | https://doaj.org/article/fb52aec78d484fa7a44a296e56c0db33 |
| رقم الأكسشن: | edsdoj.fb52aec78d484fa7a44a296e56c0db33 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 2050084X |
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| DOI: | 10.7554/eLife.91766 |