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 Qiu; Wei Jia; Wen Zhou

doi:10.1038/s41467-022-31248-w

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 journal › Journal article › peer-review

30 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 language	English
Article number	4007
Number of pages	16
Journal	Nature Communications
Volume	13
Issue number	1
DOIs	https://doi.org/10.1038/s41467-022-31248-w
Publication status	Published - 11 Jul 2022

Scopus Subject Areas

General Chemistry
General Biochemistry,Genetics and Molecular Biology
General Physics and Astronomy

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s41467-022-31248-w

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Xia, J., Zhang, J., Wu, X., Du, W., Zhu, Y., Liu, X., Liu, Z., Meng, B., Guo, J., Yang, Q., Wang, Y., Wang, Q., Feng, X., Xie, G., Shen, Y., He, Y., Xiang, J., Wu, M., An, G., ... Zhou, W. (2022). Blocking glycine utilization inhibits multiple myeloma progression by disrupting glutathione balance. Nature Communications, 13(1), Article 4007. https://doi.org/10.1038/s41467-022-31248-w

@article{81a99a2ed3354bdb928f88acc2176f13,

title = "Blocking glycine utilization inhibits multiple myeloma progression by disrupting glutathione balance",

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.",

author = "Jiliang Xia and Jingyu Zhang and Xuan Wu and Wanqing Du and Yinghong Zhu and Xing Liu and Zhenhao Liu and Bin Meng and Jiaojiao Guo and Qin Yang and Yihui Wang and Qinglin Wang and Xiangling Feng and Guoxiang Xie and Yi Shen and Yanjuan He and Juanjuan Xiang and Minghua Wu and Gang An and Lugui Qiu and Wei Jia and Wen Zhou",

note = "Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = jul,

day = "11",

doi = "10.1038/s41467-022-31248-w",

language = "English",

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journal = "Nature Communications",

issn = "2041-1723",

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Xia, J, Zhang, J, Wu, X, Du, W, Zhu, Y, Liu, X, Liu, Z, Meng, B, Guo, J, Yang, Q, Wang, Y, Wang, Q, Feng, X, Xie, G, Shen, Y, He, Y, Xiang, J, Wu, M, An, G, Qiu, L, Jia, W & Zhou, W 2022, 'Blocking glycine utilization inhibits multiple myeloma progression by disrupting glutathione balance', Nature Communications, vol. 13, no. 1, 4007. https://doi.org/10.1038/s41467-022-31248-w

TY - JOUR

T1 - Blocking glycine utilization inhibits multiple myeloma progression by disrupting glutathione balance

AU - Xia, Jiliang

AU - Zhang, Jingyu

AU - Wu, Xuan

AU - Du, Wanqing

AU - Zhu, Yinghong

AU - Liu, Xing

AU - Liu, Zhenhao

AU - Meng, Bin

AU - Guo, Jiaojiao

AU - Yang, Qin

AU - Wang, Yihui

AU - Wang, Qinglin

AU - Feng, Xiangling

AU - Xie, Guoxiang

AU - Shen, Yi

AU - He, Yanjuan

AU - Xiang, Juanjuan

AU - Wu, Minghua

AU - An, Gang

AU - Qiu, Lugui

AU - Jia, Wei

AU - Zhou, Wen

PY - 2022/7/11

Y1 - 2022/7/11

N2 - 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.

AB - 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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U2 - 10.1038/s41467-022-31248-w

DO - 10.1038/s41467-022-31248-w

M3 - Journal article

C2 - 35817773

AN - SCOPUS:85133749317

SN - 2041-1723

VL - 13

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 4007

ER -

Blocking glycine utilization inhibits multiple myeloma progression by disrupting glutathione balance

Abstract

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