新科学想法 › 文献管理 › 浏览文献

Breast Cancer-Derived Lung Metastases Show Increased Pyruvate Carboxylase-Dependent Anaplerosis

阿平添加于 2016-12-6 08:37 | 3206 次阅读 | 0 个评论

作者
Christen S, Lorendeau D, Schmieder R, Broekaert D, Metzger K, Veys K, Elia I, Buescher JM, Orth MF, Davidson SM, Grunewald TGP, De Bock K, Fendt S-M
摘要
Cellular proliferation depends on refilling the tricarboxylic acid (TCA) cycle to support biomass production (anaplerosis). The two major anaplerotic pathways in cells are pyruvate conversion to oxaloacetate via pyruvate carboxylase (PC) and glutamine conversion to alpha-ketoglutarate. Cancers often show an organ-specific reliance on either pathway. However, it remains unknown whether they adapt their mode of anaplerosis when metastasizing to a distant organ. We measured PC-dependent anaplerosis in breast-cancer-derived lung metastases compared to their primary cancers using in vivo 13C tracer analysis. We discovered that lung metastases have higher PC-dependent anaplerosis compared to primary breast cancers. Based on in vitro analysis and a mathematical model for the determination of compartment-specific metabolite concentrations, we found that mitochondrial pyruvate concentrations can promote PC-dependent anaplerosis via enzyme kinetics. In conclusion, we show that breast cancer cells proliferating as lung metastases activate PC-dependent anaplerosis in response to the lung microenvironment.
详细资料
- 关键词: (13)C tracer analysis; TCA cycle anaplerosis; breast cancer; cancer metabolism; glycolytic metabolism; lung metastasis; microenvironment; mitochondrial pyruvate concentration; pyruvate carboxylase; pyruvate metabolism
- 文献种类:期刊
- 期刊名称: Cell Reports
- 期刊缩写: Cell Rep
- 期卷页: 2016年第17卷第3期 837-848页
- 地址: Laboratory of Cellular Metabolism and Metabolic Regulation, Vesalius Research Center, VIB, Herestraat 49, 3000 Leuven, Belgium; Laboratory of Cellular Metabolism and Metabolic Regulation, Department of Oncology, KU Leuven and Leuven Cancer Institute (LKI), Herestraat 49, 3000 Leuven, Belgium. Electronic address: sarah-maria.fendt@vib-kuleuven.be
- ISBN: 2211-1247
相关链接 DOI URL
阿平的文献笔记订阅

换个地方，瘤也不再是那个瘤了