2. Academic Validation
  3. Di-methylation of CD147-K234 Promotes the Progression of NSCLC by Enhancing Lactate Export

Di-methylation of CD147-K234 Promotes the Progression of NSCLC by Enhancing Lactate Export

  • Cell Metab. 2021 Jan 5;33(1):160-173.e6. doi: 10.1016/j.cmet.2020.12.010.
Ke Wang 1,  Wan Huang 1,  Ruo Chen 1,  Peng Lin 1,  Tao Zhang 2,  Yun-Feng Ni 3,  Hao Li 1,  Jiao Wu 1,  Xiu-Xuan Sun 1,  Jie-Jie Geng 1,  Yu-Meng Zhu 1,  Gang Nan 1,  Wei Zhang 4,  Xi Chen 5,  Ping Zhu 6,  Huijie Bian 7,  Zhi-Nan Chen 8
Affiliations

Affiliations

  • 1 National Translational Science Center for Molecular Medicine and Department of Cell Biology, Fourth Military Medical University, Xi'an 710032, Shaanxi, China.
  • 2 Department of Pulmonary and Critical Care Medicine, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, Shaanxi, China.
  • 3 Department of Thoracic Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, Shaanxi, China.
  • 4 Department of Pathology, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, Shaanxi, China.
  • 5 College of Chemistry and Materials Science, Northwest University, Xi'an 710127, Shaanxi, China.
  • 6 National Translational Science Center for Molecular Medicine and Department of Cell Biology, Fourth Military Medical University, Xi'an 710032, Shaanxi, China; Department of Clinical Immunology, PLA Specialized Research Institute of Rheumatology and Immunology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi, China. Electronic address: zhuping@fmmu.edu.cn.
  • 7 National Translational Science Center for Molecular Medicine and Department of Cell Biology, Fourth Military Medical University, Xi'an 710032, Shaanxi, China. Electronic address: hjbian@fmmu.edu.cn.
  • 8 National Translational Science Center for Molecular Medicine and Department of Cell Biology, Fourth Military Medical University, Xi'an 710032, Shaanxi, China. Electronic address: znchen@fmmu.edu.cn.
PMID: 33406400 DOI: 10.1016/j.cmet.2020.12.010
Abstract

CD147 is a tumor-associated glycoprotein that regulates cell metabolism. However, CD147 methylation and its subsequent role in Cancer cell metabolism remain unclear. Here, we detect CD147 di-methylation in 16 non-small-cell lung Cancer (NSCLC) tissues using liquid chromatography-tandem mass spectrometry. CD147 is di-methylated to CD147-K234me2 by lysine methyltransferase 5A (KMT5A). The increase in KMT5A expression boosts the levels of CD147-K234me2, further promoting the interaction between CD147 and Monocarboxylate Transporter 4 (MCT4), which enhances the translocation of MCT4 from the cytoplasm to the membrane. Overexpression of CD147-K234me2 and KMT5A enhances glycolysis and lactate export in NSCLC cells. Clinical analysis shows that high CD147-K234me2 expression is significantly related to Cancer progression and overall survival, and has prognostic significance in individuals with NSCLC, especially for those in the early stages. Our findings indicate that CD147-K234me2 plays a critical role in Cancer metabolism, and it can be a highly promising therapeutic target for NSCLC.

Keywords

CD147; KMT5A; MCT4; NSCLC; di-methylation; lactate.

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