2. Academic Validation
  3. Blocking glycine utilization inhibits multiple myeloma progression by disrupting glutathione balance

Blocking glycine utilization inhibits multiple myeloma progression by disrupting glutathione balance

  • Nat Commun. 2022 Jul 11;13(1):4007. doi: 10.1038/s41467-022-31248-w.
Jiliang Xia  # 1 2 3,  Jingyu Zhang  # 1 2,  Xuan Wu 2,  Wanqing Du 4,  Yinghong Zhu 1 2,  Xing Liu 1 2,  Zhenhao Liu 1 2,  Bin Meng 1 2,  Jiaojiao Guo 2,  Qin Yang 5,  Yihui Wang 1 2,  Qinglin Wang 6,  Xiangling Feng 4,  Guoxiang Xie 7,  Yi Shen 8,  Yanjuan He 1,  Juanjuan Xiang 2,  Minghua Wu 2,  Gang An 9,  Lugui Qiu 9,  Wei Jia 10,  Wen Zhou 11 12
Affiliations

Affiliations

  • 1 Haihe Laboratory of Cell Ecosystem, State Key Laboratory of Experimental Hematology, Key Laboratory for Carcinogenesis and Invasion, Chinese Ministry of Education, Key Laboratory of Carcinogenesis, Chinese Ministry of Health, Department of Hematology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
  • 2 Cancer Research Institute, School of Basic Medical Sciences, Central South University, Changsha, Hunan, China.
  • 3 Hunan Province Key Laboratory of Tumor Cellular & Molecular Pathology, Cancer Research Institute, Hengyang Medical School, University of South China, Hengyang, Hunan, China.
  • 4 Xiangya School of Public Health, Central South University, Changsha, Hunan, China.
  • 5 Department of Hematology, Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
  • 6 Department of Laboratory Medicine, Hunan Normal University School of Medicine, Changsha, Hunan, China.
  • 7 Human Metabolomics Institute, Inc, Shenzhen, Guangdong, China.
  • 8 Department of Orthopaedic Surgery, Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
  • 9 State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, China.
  • 10 School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China.
  • 11 Haihe Laboratory of Cell Ecosystem, State Key Laboratory of Experimental Hematology, Key Laboratory for Carcinogenesis and Invasion, Chinese Ministry of Education, Key Laboratory of Carcinogenesis, Chinese Ministry of Health, Department of Hematology, Xiangya Hospital, Central South University, Changsha, Hunan, China. wenzhou@csu.edu.cn.
  • 12 Cancer Research Institute, School of Basic Medical Sciences, Central South University, Changsha, Hunan, China. wenzhou@csu.edu.cn.
  • # Contributed equally.
PMID: 35817773 DOI: 10.1038/s41467-022-31248-w
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.

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