BCKDK alters the metabolism of non-small cell lung cancer
- Author(s)
- Wang, Y; Xiao, J; Jiang, W; Zuo, D; Wang, X; Jin, Y; Qiao, L; An, H; Yang, L; Dumoulin, DW; Dempke, WCM; Best, SA; Ren, L;
- Details
- Publication Year 2021-12,Volume 10,Issue #12,Page 4459-4476
- Journal Title
- Translational Lung Cancer Research
- Abstract
- BACKGROUND: Metabolic reprogramming is a major feature of many tumors including non-small cell lung cancer (NSCLC). Branched-chain α-keto acid dehydrogenase kinase (BCKDK) plays an important role in diabetes, obesity, and other diseases. However, the function of BCKDK in NSCLC is unclear. This study aimed to explore the function of BCKDK in NSCLC. METHODS: Metabolites in the serum of patients with NSCLC and the supernatant of NSCLC cell cultures were detected using nuclear magnetic resonance (NMR) spectroscopy. Colony formation, cell proliferation, and cell apoptosis were assessed to investigate the function of BCKDK in the progression of NSCLC. Glucose uptake, lactate production, cellular oxygen consumption rate, extracellular acidification rate, and reactive oxygen species (ROS) were measured to examine the function of BCKDK in glucose metabolism. The expression of BCKDK was measured using reverse transcriptase-polymerase chain reaction, western blot, and immunohistochemical assay. RESULTS: Compared with healthy controls and postoperative NSCLC patients, increased branched-chain amino acid (BCAA) and decreased citrate were identified in the serum of preoperative NSCLC patients. Upregulation of BCKDK affected the metabolism of BCAAs and citrate in NSCLC cells. Knockout of BCKDK decreased the proliferation and exacerbated apoptosis of NSCLC cells ex vivo, while increased oxidative phosphorylation and, ROS levels, and inhibited glycolysis. CONCLUSIONS: BCKDK may influence glycolysis and oxidative phosphorylation by regulating the degradation of BCAA and citrate, thereby affecting the progression of NSCLC.
- Publisher
- AME Publishing Company
- Keywords
- Branched-chain α-keto acid dehydrogenase kinase (BCKDK); branched-chain amino acids (BCAAs); citrate; glucose metabolism; non-small cell lung cancer (NSCLC); (available at https://dx.doi.org/10.21037/tlcr-21-885). The authors have no; conflicts of interest to declare.
- Research Division(s)
- Personalised Oncology
- PubMed ID
- 5070754
- Publisher's Version
- https://doi.org/10.21037/tlcr-21-885
- Open Access at Publisher's Site
https://doi.org/10.21037/tlcr-21-885- Terms of Use/Rights Notice
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Creation Date: 2022-02-07 10:12:28
Last Modified: 2022-02-08 02:26:07