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Metabolic Reprogramming of Mammary Epithelial Cells during TGF-β-Induced Epithelial-to-Mesenchymal Transition.

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机构: [1]Oncode Institute and Cell Chemical Biology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands. [2]Institute of Rare Diseases, West China Hospital, Sichuan University, Chengdu 610041, China. [3]Center for Proteomics and Metabolomics, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.
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The cytokine transforming growth factor-β (TGF-β) can induce normal breast epithelial cells to take on a mesenchymal phenotype, termed epithelial-to-mesenchymal transition (EMT). While the transcriptional and proteomic changes during TGF-β-induced EMT have been described, the metabolic rewiring that occurs in epithelial cells undergoing EMT is not well understood. Here, we quantitively analyzed the TGF-β-induced metabolic reprogramming during EMT of non-transformed NMuMG mouse mammary gland epithelial cells using nuclear magnetic resonance (NMR) spectroscopy. We found that TGF-β elevates glycolytic and tricarboxylic acid (TCA)-cycle activity and increases glutaminolysis. Additionally, TGF-β affects the hexosamine pathway, arginine-proline metabolism, the cellular redox state, and strongly affects choline metabolism during EMT. TGF-β was found to induce phosphocholine production. A kinase inhibitor RSM-93A that inhibits choline kinase α (CHKα) mitigated TGF-β-induced changes associated with EMT, i.e., increased filamentous (F)-actin stress fiber formation and N-Cadherin mesenchymal marker expression.

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出版当年[2021]版:
大类 | 3 区 生物学
小类 | 3 区 生化与分子生物学
最新[2023]版:
大类 | 3 区 生物学
小类 | 3 区 生化与分子生物学
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第一作者机构: [1]Oncode Institute and Cell Chemical Biology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands. [2]Institute of Rare Diseases, West China Hospital, Sichuan University, Chengdu 610041, China.
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