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Blocking glycine utilization inhibits multiple myeloma progression by disrupting glutathione balance

Author

Listed:
  • Jiliang Xia

    (Central South University
    Central South University
    University of South China)

  • Jingyu Zhang

    (Central South University
    Central South University)

  • Xuan Wu

    (Central South University)

  • Wanqing Du

    (Central South University)

  • Yinghong Zhu

    (Central South University
    Central South University)

  • Xing Liu

    (Central South University
    Central South University)

  • Zhenhao Liu

    (Central South University
    Central South University)

  • Bin Meng

    (Central South University
    Central South University)

  • Jiaojiao Guo

    (Central South University)

  • Qin Yang

    (Central South University)

  • Yihui Wang

    (Central South University
    Central South University)

  • Qinglin Wang

    (Hunan Normal University School of Medicine)

  • Xiangling Feng

    (Central South University)

  • Guoxiang Xie

    (Human Metabolomics Institute, Inc)

  • Yi Shen

    (Central South University)

  • Yanjuan He

    (Central South University)

  • Juanjuan Xiang

    (Central South University)

  • Minghua Wu

    (Central South University)

  • Gang An

    (Chinese Academy of Medical Science & Peking Union Medical College)

  • Lugui Qiu

    (Chinese Academy of Medical Science & Peking Union Medical College)

  • Wei Jia

    (Hong Kong Baptist University, Kowloon Tong)

  • Wen Zhou

    (Central South University
    Central South University)

Abstract

Metabolites in the tumor microenvironment are a critical factor for tumor progression. However, the lack of knowledge about the metabolic profile in the bone marrow (BM) microenvironment of multiple myeloma (MM) limits our understanding of MM progression. Here, we show that the glycine concentration in the BM microenvironment is elevated due to bone collagen degradation mediated by MM cell-secreted matrix metallopeptidase 13 (MMP13), while the elevated glycine level is linked to MM progression. MM cells utilize the channel protein solute carrier family 6 member 9 (SLC6A9) to absorb extrinsic glycine subsequently involved in the synthesis of glutathione (GSH) and purines. Inhibiting glycine utilization via SLC6A9 knockdown or the treatment with betaine suppresses MM cell proliferation and enhances the effects of bortezomib on MM cells. Together, we identify glycine as a key metabolic regulator of MM, unveil molecular mechanisms governing MM progression, and provide a promising therapeutic strategy for MM treatment.

Suggested Citation

  • Jiliang Xia & Jingyu Zhang & Xuan Wu & Wanqing Du & Yinghong Zhu & Xing Liu & Zhenhao Liu & Bin Meng & Jiaojiao Guo & Qin Yang & Yihui Wang & Qinglin Wang & Xiangling Feng & Guoxiang Xie & Yi Shen & Y, 2022. "Blocking glycine utilization inhibits multiple myeloma progression by disrupting glutathione balance," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31248-w
    DOI: 10.1038/s41467-022-31248-w
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    Cited by:

    1. Chunmei Kuang & Meijuan Xia & Gang An & CuiCui Liu & Cong Hu & Jingyu Zhang & Zhenhao Liu & Bin Meng & Pei Su & Jiliang Xia & Jiaojiao Guo & Yinghong Zhu & Xing Liu & Xuan Wu & Yi Shen & Xiangling Fen, 2023. "Excessive serine from the bone marrow microenvironment impairs megakaryopoiesis and thrombopoiesis in Multiple Myeloma," Nature Communications, Nature, vol. 14(1), pages 1-18, December.

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