دورية أكاديمية
Metastatic breast cancer cells are metabolically reprogrammed to maintain redox homeostasis during metastasis
| العنوان: | Metastatic breast cancer cells are metabolically reprogrammed to maintain redox homeostasis during metastasis |
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| المؤلفون: | Marco Biondini, Camille Lehuédé, Sébastien Tabariès, Matthew G. Annis, Alain Pacis, Eric H. Ma, Christine Tam, Brian E. Hsu, Yannick Audet-Delage, Afnan Abu-Thuraia, Charlotte Girondel, Valerie Sabourin, Stephanie P. Totten, Mariana de Sá Tavares Russo, Gaëlle Bridon, Daina Avizonis, Marie-Christine Guiot, Julie St-Pierre, Josie Ursini-Siegel, Russell Jones, Peter M. Siegel |
| المصدر: | Redox Biology, Vol 75, Iss , Pp 103276- (2024) |
| بيانات النشر: | Elsevier, 2024. |
| سنة النشر: | 2024 |
| المجموعة: | LCC:Medicine (General) LCC:Biology (General) |
| مصطلحات موضوعية: | Glutathione, Breast cancer, Liver metastasis, Oxidative stress, Metabolism, Glycolysis, Medicine (General), R5-920, Biology (General), QH301-705.5 |
| الوصف: | Metabolic rewiring is essential for tumor growth and progression to metastatic disease, yet little is known regarding how cancer cells modify their acquired metabolic programs in response to different metastatic microenvironments. We have previously shown that liver-metastatic breast cancer cells adopt an intrinsic metabolic program characterized by increased HIF-1α activity and dependence on glycolysis. Here, we confirm by in vivo stable isotope tracing analysis (SITA) that liver-metastatic breast cancer cells retain a glycolytic profile when grown as mammary tumors or liver metastases. However, hepatic metastases exhibit unique metabolic adaptations including elevated expression of genes involved in glutathione (GSH) biosynthesis and reactive oxygen species (ROS) detoxification when compared to mammary tumors. Accordingly, breast-cancer-liver-metastases exhibited enhanced de novo GSH synthesis. Confirming their increased capacity to mitigate ROS-mediated damage, liver metastases display reduced levels of 8-Oxo-2′-deoxyguanosine. Depletion of the catalytic subunit of the rate-limiting enzyme in glutathione biosynthesis, glutamate-cysteine ligase (GCLC), strongly reduced the capacity of breast cancer cells to form liver metastases, supporting the importance of these distinct metabolic adaptations.Loss of GCLC also affected the early steps of the metastatic cascade, leading to decreased numbers of circulating tumor cells (CTCs) and impaired metastasis to the liver and the lungs. Altogether, our results indicate that GSH metabolism could be targeted to prevent the dissemination of breast cancer cells. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2213-2317 |
| Relation: | http://www.sciencedirect.com/science/article/pii/S2213231724002544; https://doaj.org/toc/2213-2317 |
| DOI: | 10.1016/j.redox.2024.103276 |
| URL الوصول: | https://doaj.org/article/9541bdda466b464aac43f308bd0b1d8e |
| رقم الأكسشن: | edsdoj.9541bdda466b464aac43f308bd0b1d8e |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 22132317 |
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| DOI: | 10.1016/j.redox.2024.103276 |