Blocking glycine utilization inhibits multiple myeloma progression by disrupting glutathione balance

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, Yanjuan He, Juanjuan Xiang, Minghua Wu, Gang An, Lugui QiuWei Jia, Wen Zhou*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

19 Citations (Scopus)

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.

Original languageEnglish
Article number4007
Number of pages16
JournalNature Communications
Volume13
DOIs
Publication statusPublished - 11 Jul 2022

Scopus Subject Areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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