DLST-dependence dictates metabolic heterogeneity in TCA-cycle usage among triple-negative breast cancer
| العنوان: | DLST-dependence dictates metabolic heterogeneity in TCA-cycle usage among triple-negative breast cancer |
|---|---|
| المؤلفون: | Xiaoyu Zhang, Ching-Ti Liu, Hanfei Xu, Justin English, Wei-Xing Zong, Theodoros Karantanos, Sovannarith Korm, Ning Shen, Dun Li, Orian S. Shirihai, Eleni Ritou, Andrew Lam, Hui Feng |
| المصدر: | Communications Biology, Vol 4, Iss 1, Pp 1-11 (2021) Communications Biology |
| بيانات النشر: | Springer Science and Business Media LLC, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Dihydrolipoamide, QH301-705.5, Glutamine, Citric Acid Cycle, Medicine (miscellaneous), Triple Negative Breast Neoplasms, Biology, Article, General Biochemistry, Genetics and Molecular Biology, Breast cancer, Metabolomics, Cell Line, Tumor, medicine, Humans, Glycolysis, Biology (General), Triple-negative breast cancer, Cell Proliferation, chemistry.chemical_classification, Reactive oxygen species, Cell growth, Cell Cycle, medicine.disease, Cancer metabolism, chemistry, Cancer research, General Agricultural and Biological Sciences, Acyltransferases, medicine.drug |
| الوصف: | Triple-negative breast cancer (TNBC) is traditionally considered a glycolytic tumor with a poor prognosis while lacking targeted therapies. Here we show that high expression of dihydrolipoamide S-succinyltransferase (DLST), a tricarboxylic acid (TCA) cycle enzyme, predicts poor overall and recurrence-free survival among TNBC patients. DLST depletion suppresses growth and induces death in subsets of human TNBC cell lines, which are capable of utilizing glutamine anaplerosis. Metabolomics profiling reveals significant changes in the TCA cycle and reactive oxygen species (ROS) related pathways for sensitive but not resistant TNBC cells. Consequently, DLST depletion in sensitive TNBC cells increases ROS levels while N-acetyl-L-cysteine partially rescues cell growth. Importantly, suppression of the TCA cycle through DLST depletion or CPI-613, a drug currently in clinical trials for treating other cancers, decreases the burden and invasion of these TNBC. Together, our data demonstrate differential TCA-cycle usage in TNBC and provide therapeutic implications for the DLST-dependent subsets. Shen and Korm et al. investigate the role of dihydrolipoamide S-succinyltransferase (DLST), a tricarboxylic acid (TCA) cycle enzyme, in the metabolic heterogeneity of triple negative breast cancer (TNBC) cell lines. They show that either depletion or inhibition of DLST in the dependent cells leads to decreased invasion and metastasis in vitro and in vivo. |
| تدمد: | 2399-3642 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2f53bb966ebeeaffc4e21368572786ac https://doi.org/10.1038/s42003-021-02805-8 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....2f53bb966ebeeaffc4e21368572786ac |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 23993642 |
|---|