دورية أكاديمية
p66ShcA promotes malignant breast cancer phenotypes by alleviating energetic and oxidative stress
العنوان: | p66ShcA promotes malignant breast cancer phenotypes by alleviating energetic and oxidative stress |
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المؤلفون: | Kyle Lewis, Rachel La Selva, Elias Maldonado, Matthew G. Annis, Ouafa Najyb, Eduardo Cepeda Cañedo, Stephanie Totten, Steven Hébert, Valérie Sabourin, Caitlynn Mirabelli, Emma Ciccolini, Camille Lehuédé, Luc Choinière, Mariana Russo, Daina Avizonis, Morag Park, Julie St-Pierre, Claudia L. Kleinman, Peter M. Siegel, Josie Ursini-Siegel |
المصدر: | Redox Biology, Vol 70, Iss , Pp 103028- (2024) |
بيانات النشر: | Elsevier, 2024. |
سنة النشر: | 2024 |
المجموعة: | LCC:Medicine (General) LCC:Biology (General) |
مصطلحات موضوعية: | p66ShcA, Breast cancer, Oxidative stress, Metabolic plasticity, Glutathione, Anoikis, Medicine (General), R5-920, Biology (General), QH301-705.5 |
الوصف: | Significant efforts have focused on identifying targetable genetic drivers that support the growth of solid tumors and/or increase metastatic ability. During tumor development and progression to metastatic disease, physiological and pharmacological selective pressures influence parallel adaptive strategies within cancer cell sub-populations. Such adaptations allow cancer cells to withstand these stressful microenvironments. This Darwinian model of stress adaptation often prevents durable clinical responses and influences the emergence of aggressive cancers with increased metastatic fitness. However, the mechanisms contributing to such adaptive stress responses are poorly understood. We now demonstrate that the p66ShcA redox protein, itself a ROS inducer, is essential for survival in response to physiological stressors, including anchorage independence and nutrient deprivation, in the context of poor outcome breast cancers. Mechanistically, we show that p66ShcA promotes both glucose and glutamine metabolic reprogramming in breast cancer cells, to increase their capacity to engage catabolic metabolism and support glutathione synthesis. In doing so, chronic p66ShcA exposure contributes to adaptive stress responses, providing breast cancer cells with sufficient ATP and redox balance needed to withstand such transient stressed states. Our studies demonstrate that p66ShcA functionally contributes to the maintenance of aggressive phenotypes and the emergence of metastatic disease by forcing breast tumors to adapt to chronic and moderately elevated levels of oxidative stress. |
نوع الوثيقة: | article |
وصف الملف: | electronic resource |
اللغة: | English |
تدمد: | 2213-2317 |
Relation: | http://www.sciencedirect.com/science/article/pii/S2213231724000041; https://doaj.org/toc/2213-2317 |
DOI: | 10.1016/j.redox.2024.103028 |
URL الوصول: | https://doaj.org/article/8bcb1cc7a7684f09b3d926e68c5a0e4c |
رقم الأكسشن: | edsdoj.8bcb1cc7a7684f09b3d926e68c5a0e4c |
قاعدة البيانات: | Directory of Open Access Journals |
تدمد: | 22132317 |
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DOI: | 10.1016/j.redox.2024.103028 |