Phosphoglycerate dehydrogenase promotes proliferation and bortezomib resistance through increasing reduced glutathione synthesis in multiple myeloma
Xuan Wu
Department of Hematology, Xiangya Hospital, Central South University, Changsha, Hunan, China
Key Laboratory of Carcinogenesis of the Chinese Ministry of Health and the Key Laboratory of Carcinogenesis and Cancer Invasion of Chinese Ministry of Education, Cancer Research Institute, School of Basic Medical Sciences, Central South University, Changsha, Hunan, China
These authors contributed equally to this work.Search for more papers by this authorJiliang Xia
Department of Hematology, Xiangya Hospital, Central South University, Changsha, Hunan, China
Key Laboratory of Carcinogenesis of the Chinese Ministry of Health and the Key Laboratory of Carcinogenesis and Cancer Invasion of Chinese Ministry of Education, Cancer Research Institute, School of Basic Medical Sciences, Central South University, Changsha, Hunan, China
These authors contributed equally to this work.Search for more papers by this authorJingyu Zhang
Key Laboratory of Carcinogenesis of the Chinese Ministry of Health and the Key Laboratory of Carcinogenesis and Cancer Invasion of Chinese Ministry of Education, Cancer Research Institute, School of Basic Medical Sciences, Central South University, Changsha, Hunan, China
Search for more papers by this authorYinghong Zhu
Key Laboratory of Carcinogenesis of the Chinese Ministry of Health and the Key Laboratory of Carcinogenesis and Cancer Invasion of Chinese Ministry of Education, Cancer Research Institute, School of Basic Medical Sciences, Central South University, Changsha, Hunan, China
Search for more papers by this authorYangbowen Wu
Xiangya School of Public Health, Central South University, Changsha, Hunan, China
Search for more papers by this authorJiaojiao Guo
Key Laboratory of Carcinogenesis of the Chinese Ministry of Health and the Key Laboratory of Carcinogenesis and Cancer Invasion of Chinese Ministry of Education, Cancer Research Institute, School of Basic Medical Sciences, Central South University, Changsha, Hunan, China
Search for more papers by this authorShilian Chen
Key Laboratory of Carcinogenesis of the Chinese Ministry of Health and the Key Laboratory of Carcinogenesis and Cancer Invasion of Chinese Ministry of Education, Cancer Research Institute, School of Basic Medical Sciences, Central South University, Changsha, Hunan, China
Search for more papers by this authorQian Lei
Key Laboratory of Carcinogenesis of the Chinese Ministry of Health and the Key Laboratory of Carcinogenesis and Cancer Invasion of Chinese Ministry of Education, Cancer Research Institute, School of Basic Medical Sciences, Central South University, Changsha, Hunan, China
Search for more papers by this authorBin Meng
Key Laboratory of Carcinogenesis of the Chinese Ministry of Health and the Key Laboratory of Carcinogenesis and Cancer Invasion of Chinese Ministry of Education, Cancer Research Institute, School of Basic Medical Sciences, Central South University, Changsha, Hunan, China
Search for more papers by this authorChunmei Kuang
Key Laboratory of Carcinogenesis of the Chinese Ministry of Health and the Key Laboratory of Carcinogenesis and Cancer Invasion of Chinese Ministry of Education, Cancer Research Institute, School of Basic Medical Sciences, Central South University, Changsha, Hunan, China
Search for more papers by this authorXiangling Feng
Xiangya School of Public Health, Central South University, Changsha, Hunan, China
Search for more papers by this authorYanjuan He
Department of Hematology, Xiangya Hospital, Central South University, Changsha, Hunan, China
Search for more papers by this authorYi Shen
Department of Orthopaedic Surgery, Second Xiangya Hospital, Central South University, Changsha, Hunan, China
Search for more papers by this authorXin Li
Department of Hematology, Third Xiangya Hospital, Central South University, Changsha, Hunan, China
Search for more papers by this authorLugui Qiu
State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, China
Search for more papers by this authorCorresponding Author
Guancheng Li
Department of Hematology, Xiangya Hospital, Central South University, Changsha, Hunan, China
Key Laboratory of Carcinogenesis of the Chinese Ministry of Health and the Key Laboratory of Carcinogenesis and Cancer Invasion of Chinese Ministry of Education, Cancer Research Institute, School of Basic Medical Sciences, Central South University, Changsha, Hunan, China
Correspondence: Wen Zhou and Guancheng Li, Department of Hematology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
E-mails: [email protected]; [email protected]
Search for more papers by this authorCorresponding Author
Wen Zhou
Department of Hematology, Xiangya Hospital, Central South University, Changsha, Hunan, China
Key Laboratory of Carcinogenesis of the Chinese Ministry of Health and the Key Laboratory of Carcinogenesis and Cancer Invasion of Chinese Ministry of Education, Cancer Research Institute, School of Basic Medical Sciences, Central South University, Changsha, Hunan, China
Correspondence: Wen Zhou and Guancheng Li, Department of Hematology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
E-mails: [email protected]; [email protected]
Search for more papers by this authorXuan Wu
Department of Hematology, Xiangya Hospital, Central South University, Changsha, Hunan, China
Key Laboratory of Carcinogenesis of the Chinese Ministry of Health and the Key Laboratory of Carcinogenesis and Cancer Invasion of Chinese Ministry of Education, Cancer Research Institute, School of Basic Medical Sciences, Central South University, Changsha, Hunan, China
These authors contributed equally to this work.Search for more papers by this authorJiliang Xia
Department of Hematology, Xiangya Hospital, Central South University, Changsha, Hunan, China
Key Laboratory of Carcinogenesis of the Chinese Ministry of Health and the Key Laboratory of Carcinogenesis and Cancer Invasion of Chinese Ministry of Education, Cancer Research Institute, School of Basic Medical Sciences, Central South University, Changsha, Hunan, China
These authors contributed equally to this work.Search for more papers by this authorJingyu Zhang
Key Laboratory of Carcinogenesis of the Chinese Ministry of Health and the Key Laboratory of Carcinogenesis and Cancer Invasion of Chinese Ministry of Education, Cancer Research Institute, School of Basic Medical Sciences, Central South University, Changsha, Hunan, China
Search for more papers by this authorYinghong Zhu
Key Laboratory of Carcinogenesis of the Chinese Ministry of Health and the Key Laboratory of Carcinogenesis and Cancer Invasion of Chinese Ministry of Education, Cancer Research Institute, School of Basic Medical Sciences, Central South University, Changsha, Hunan, China
Search for more papers by this authorYangbowen Wu
Xiangya School of Public Health, Central South University, Changsha, Hunan, China
Search for more papers by this authorJiaojiao Guo
Key Laboratory of Carcinogenesis of the Chinese Ministry of Health and the Key Laboratory of Carcinogenesis and Cancer Invasion of Chinese Ministry of Education, Cancer Research Institute, School of Basic Medical Sciences, Central South University, Changsha, Hunan, China
Search for more papers by this authorShilian Chen
Key Laboratory of Carcinogenesis of the Chinese Ministry of Health and the Key Laboratory of Carcinogenesis and Cancer Invasion of Chinese Ministry of Education, Cancer Research Institute, School of Basic Medical Sciences, Central South University, Changsha, Hunan, China
Search for more papers by this authorQian Lei
Key Laboratory of Carcinogenesis of the Chinese Ministry of Health and the Key Laboratory of Carcinogenesis and Cancer Invasion of Chinese Ministry of Education, Cancer Research Institute, School of Basic Medical Sciences, Central South University, Changsha, Hunan, China
Search for more papers by this authorBin Meng
Key Laboratory of Carcinogenesis of the Chinese Ministry of Health and the Key Laboratory of Carcinogenesis and Cancer Invasion of Chinese Ministry of Education, Cancer Research Institute, School of Basic Medical Sciences, Central South University, Changsha, Hunan, China
Search for more papers by this authorChunmei Kuang
Key Laboratory of Carcinogenesis of the Chinese Ministry of Health and the Key Laboratory of Carcinogenesis and Cancer Invasion of Chinese Ministry of Education, Cancer Research Institute, School of Basic Medical Sciences, Central South University, Changsha, Hunan, China
Search for more papers by this authorXiangling Feng
Xiangya School of Public Health, Central South University, Changsha, Hunan, China
Search for more papers by this authorYanjuan He
Department of Hematology, Xiangya Hospital, Central South University, Changsha, Hunan, China
Search for more papers by this authorYi Shen
Department of Orthopaedic Surgery, Second Xiangya Hospital, Central South University, Changsha, Hunan, China
Search for more papers by this authorXin Li
Department of Hematology, Third Xiangya Hospital, Central South University, Changsha, Hunan, China
Search for more papers by this authorLugui Qiu
State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, China
Search for more papers by this authorCorresponding Author
Guancheng Li
Department of Hematology, Xiangya Hospital, Central South University, Changsha, Hunan, China
Key Laboratory of Carcinogenesis of the Chinese Ministry of Health and the Key Laboratory of Carcinogenesis and Cancer Invasion of Chinese Ministry of Education, Cancer Research Institute, School of Basic Medical Sciences, Central South University, Changsha, Hunan, China
Correspondence: Wen Zhou and Guancheng Li, Department of Hematology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
E-mails: [email protected]; [email protected]
Search for more papers by this authorCorresponding Author
Wen Zhou
Department of Hematology, Xiangya Hospital, Central South University, Changsha, Hunan, China
Key Laboratory of Carcinogenesis of the Chinese Ministry of Health and the Key Laboratory of Carcinogenesis and Cancer Invasion of Chinese Ministry of Education, Cancer Research Institute, School of Basic Medical Sciences, Central South University, Changsha, Hunan, China
Correspondence: Wen Zhou and Guancheng Li, Department of Hematology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
E-mails: [email protected]; [email protected]
Search for more papers by this authorSummary
The serine synthesis pathway (SSP) is active in multiple cancers. Previous study has shown that bortezomib (BTZ) resistance is associated with an increase in the SSP in multiple myeloma (MM) cells; however, the underlying mechanisms of SSP-induced BTZ resistance remain unclear. In this study, we found that phosphoglycerate dehydrogenase (PHGDH), the first rate-limiting enzyme in the SSP, was significantly elevated in CD138+ cells derived from patients with relapsed MM. Moreover, high PHGDH conferred inferior survival in MM. We also found that overexpression of PHDGH in MM cells led to increased cell growth, tumour formation, and resistance to BTZ in vitro and in vivo, while inhibition of PHGDH by short hairpin RNA or NCT-503, a specific inhibitor of PHGDH, inhibited cell growth and BTZ resistance in MM cells. Subsequent mechanistic studies demonstrated PHGDH decreased reactive oxygen species (ROS) through increasing reduced glutathione (GSH) synthesis, thereby promoting cell growth and BTZ resistance in MM cells. Furthermore, adding GSH to PHGDH silenced MM cells reversed S phase arrest and BTZ-induced cell death. These findings support a mechanism in which PHGDH promotes proliferation and BTZ resistance through increasing GSH synthesis in MM cells. Therefore, targeting PHGDH is a promising strategy for MM therapy.
Conflict of interest
The authors have no conflicts of interest to disclose.
Supporting Information
| Filename | Description |
|---|---|
| bjh16503-sup-0001-FigS1.pdfPDF document, 172.2 KB |
Fig S1. PHGDH level is positively correlated with bortezomib (BTZ) resistance in MM cells. (A) The detailed data of the enrichment analysis of metabolic pathways. (B) The abundance ratios of serine, glycine, and threonine between conditioned mediums (CM) derived from KMS28-PE and ARP1 MM cell lines and fresh medium (FM). (C) Identification of drug-resistant MM cell lines (BTZ-resistant cell line ANBL6 BR and dexamethasone-resistant cell line MM1.R). nsP > 0·05, *P < 0·05, **P < 0·01, ***P < 0·001. (D) The protein levels of PHGDH and β-actin in ARP1, KMS28-PE, MM1.S, OCI-My5, KMS11, and ANBL6 MM cell lines were examined by Western blotting. (E) CCK-8 assays of ARP1, KMS28-PE, MM1.S, OCI-My5, KMS11, and ANBL6 MM cell lines treated with different doses of BTZ (0, 1·25, 2·5, 5, 10, 20, 40, 80, 160 nmol/l) for 2 days. (F) The correlation between PHGDH protein levels and IC50 values of BTZ in ARP1, KMS28-PE, MM1.S, OCI-My5, KMS11 and ANBL6 MM cell lines. |
| bjh16503-sup-0002-FigS2.pdfPDF document, 209.6 KB |
Fig S2. Knockdown PHGDH by shRNA2 inhibits MM cell growth and induces MM cell apoptosis. (A) Western blots confirm PHGDH was knocked down by PHGDH shRNA2 in both ARP1 and KMS28-PE MM cell lines. (B) Growth curves of KMS28-PE Ctrl, KMS28-PE PHGDH shRNA2, ARP1 Ctrl, and ARP1 PHGDH shRNA2 MM cell lines by counting alive cells after trypan blue exclusion. nsP > 0·05, *P < 0·05, **P < 0·01. (C) Cell cycle assays of KMS28-PE Ctrl, KMS28-PE PHGDH shRNA1, ARP1 Ctrl, and ARP1 PHGDH shRNA1 MM cell lines. Assessment of cell apoptosis by using PE-Annexin V/7-AAD staining in KMS28-PE Ctrl, KMS28-PE PHGDH shRNA2, ARP1 Ctrl, and ARP1 PHGDH shRNA2 MM cell lines. |
| bjh16503-sup-0003-FigS3.pdfPDF document, 188.7 KB |
Fig S3. Overexpression of PHGDH prevents bortezomib (BTZ) induced ER-stress and autophagy. (A) Cell cycle assays of KMS28-PE empty vector (EV), KMS28-PE PHGDH overexpressing (OE), ARP1 EV, and ARP1 PHGDH OE MM cell lines. (B) Western bots of XBP1s, LC3B, and β-actin in KMS28-PE EV, KMS28-PE PHGDH OE, ARP1 EV, and ARP1 PHGDH OE after treatment with or without BTZ (10 nmol/l) for 2 days. |
| bjh16503-sup-0004-FigS4.pdfPDF document, 177 KB |
Fig S4. Addition of glycine or GSH promotes bortezomib (BTZ) resistance in ANBL6. (A) ANBL6 MM cells were pre-treated with glycine (10 mg/ml) or GSH (2 mmol/l) for 24 h followed by BTZ treatment for additional 48 h, then CCK-8 assay was performed to examine cell viability. nsP > 0·05, **P < 0·01, ***P < 0·001. (B) Cell cycle assays of KMS28-PE PHGDH shRNA1 and ARP1 PHGDH shRNA1 treated with or without GSH (2 mmol/l) for 2 days. |
| bjh16503-sup-0005-TableS1.docWord document, 86 KB |
Table SI. The detailed data of the metabolic pathway analysis. |
| bjh16503-sup-0006-TableS2.docWord document, 73 KB |
Table SII. Clinical characteristics of healthy donors and patients with MM. |
| bjh16503-sup-0007-TableS3.docWord document, 31.5 KB |
Table SIII. The list of primer sequences. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
References
- Achouri, Y., Rider, M.H., Schaftingen, E.V. & Robbi, M. (1997) Cloning, sequencing and expression of rat liver 3-phosphoglycerate dehydrogenase. The Biochemical Journal, 323, 365–370.
- Acuna-Hidalgo, R., Schanze, D., Kariminejad, A., Nordgren, A., Kariminejad, M.H., Conner, P., Grigelioniene, G., Nilsson, D., Nordenskjold, M., Wedell, A., Freyer, C., Wredenberg, A., Wieczorek, D., Gillessen-Kaesbach, G., Kayserili, H., Elcioglu, N., Ghaderi-Sohi, S., Goodarzi, P., Setayesh, H., van de Vorst, M., Steehouwer, M., Pfundt, R., Krabichler, B., Curry, C., MacKenzie, M.G., Boycott, K.M., Gilissen, C., Janecke, A.R., Hoischen, A. & Zenker, M. (2014) Neu-Laxova syndrome is a heterogeneous metabolic disorder caused by defects in enzymes of the L-serine biosynthesis pathway. American Journal of Human Genetics, 95, 285–293.
- Al-Eisawi, Z., Beale, P., Chan, C., Yu, J.Q. & Huq, F. (2013) Carboplatin and oxaliplatin in sequenced combination with bortezomib in ovarian tumour models. Journal of Ovarian Research, 6, 78.
- Castello, A., Fischer, B., Frese, C.K., Horos, R., Alleaume, A.M., Foehr, S., Curk, T., Krijgsveld, J. & Hentze, M.W. (2016) Comprehensive identification of RNA-binding domains in human cells. Molecular Cell, 63, 696–710.
- DeBerardinis, R.J. (2011) Serine metabolism: some tumors take the road less traveled. Cell Metabolism, 14, 285–286.
- DeNicola, G.M., Chen, P.H., Mullarky, E., Sudderth, J.A., Hu, Z., Wu, D., Tang, H., Xie, Y., Asara, J.M., Huffman, K.E., Wistuba, I.I., Minna, J.D., DeBerardinis, R.J. & Cantley, L.C. (2015) NRF2 regulates serine biosynthesis in non-small cell lung cancer. Nature Genetics, 47, 1475–1481.
- Dong, H., Chen, L., Chen, X., Gu, H., Gao, G., Gao, Y. & Dong, B. (2009) Dysregulation of unfolded protein response partially underlies proapoptotic activity of bortezomib in multiple myeloma cells. Leukaemia & Lymphoma, 50, 974–984.
- Feng, R., Oton, A., Mapara, M.Y., Anderson, G., Belani, C. & Lentzsch, S. (2007) The histone deacetylase inhibitor, PXD101, potentiates bortezomib-induced anti-multiple myeloma effect by induction of oxidative stress and DNA damage. British Journal of Haematology, 139, 385–397.
- Galluzzi, L., Kepp, O., Vander Heiden, M.G. & Kroemer, G. (2013) Metabolic targets for cancer therapy. Nature Reviews Drug Discovery, 12, 829–846.
- Kyle, R.A. & Rajkumar, S.V. (2008) Multiple myeloma. Blood, 111, 2962–2972.
- Locasale, J.W., Grassian, A.R., Melman, T., Lyssiotis, C.A., Mattaini, K.R., Bass, A.J., Heffron, G., Metallo, C.M., Muranen, T., Sharfi, H., Sasaki, A.T., Anastasiou, D., Mullarky, E., Vokes, N.I., Sasaki, M., Beroukhim, R., Stephanopoulos, G., Ligon, A.H., Meyerson, M., Richardson, A.L., Chin, L., Wagner, G., Asara, J.M., Brugge, J.S., Cantley, L.C. & Vander Heiden, M.G. (2011) Phosphoglycerate dehydrogenase diverts glycolytic flux and contributes to oncogenesis. Nature Genetics, 43, 869–874.
- Lu, J., Zhou, J., Bao, Y., Chen, T., Zhang, Y., Zhao, A., Qiu, Y., Xie, G., Wang, C., Jia, W. & Jia, W. (2012) Serum metabolic signatures of fulminant type 1 diabetes. Journal of Proteome Research, 11, 4705–4711.
- Ma, X., Li, B., Liu, J., Fu, Y. & Luo, Y. (2019) Phosphoglycerate dehydrogenase promotes pancreatic cancer development by interacting with eIF4A1 and eIF4E. Journal of Experimental & Clinical Cancer Research, 38, 66.
- Maddocks, O.D.K., Athineos, D., Cheung, E.C., Lee, P., Zhang, T., van den Broek, N.J.F., Mackay, G.M., Labuschagne, C.F., Gay, D., Kruiswijk, F., Blagih, J., Vincent, D.F., Campbell, K.J., Ceteci, F., Sansom, O.J., Blyth, K. & Vousden, K.H. (2017) Modulating the therapeutic response of tumours to dietary serine and glycine starvation. Nature, 544, 372–376.
- Maiso, P., Huynh, D., Moschetta, M., Sacco, A., Aljawai, Y., Mishima, Y., Asara, J.M., Roccaro, A.M., Kimmelman, A.C. & Ghobrial, I.M. (2015) Metabolic signature identifies novel targets for drug resistance in multiple myeloma. Cancer Research, 75, 2071–2082.
- Malhotra, J.D. & Kaufman, R.J. (2007) Endoplasmic reticulum stress and oxidative stress: a vicious cycle or a double-edged sword? Antioxidants & Redox Signaling, 9, 2277–2293.
- Mattaini, K.R., Sullivan, M.R. & Vander Heiden, M.G. (2016) The importance of serine metabolism in cancer. Journal of Cell Biology, 214, 249–257.
- Mullarky, E., Lucki, N.C., Beheshti Zavareh, R., Anglin, J.L., Gomes, A.P., Nicolay, B.N., Wong, J.C., Christen, S., Takahashi, H., Singh, P.K., Blenis, J., Warren, J.D., Fendt, S.M., Asara, J.M., DeNicola, G.M., Lyssiotis, C.A., Lairson, L.L. & Cantley, L.C. (2016) Identification of a small molecule inhibitor of 3-phosphoglycerate dehydrogenase to target serine biosynthesis in cancers. Proceedings of the National Academy of Sciences of the United States of America, 113, 1778–1783.
- Obeng, E.A., Carlson, L.M., Gutman, D.M., Harrington, W.J. Jr, Lee, K.P. & Boise, L.H. (2006) Proteasome inhibitors induce a terminal unfolded protein response in multiple myeloma cells. Blood, 107, 4907–4916.
- Orlowski, R.Z. (2013) Novel agents for multiple myeloma to overcome resistance in phase III clinical trials. Seminars in Oncology, 40, 634–651.
- Ou, Y., Wang, S.J., Jiang, L., Zheng, B. & Gu, W. (2015) p53 Protein-mediated regulation of phosphoglycerate dehydrogenase (PHGDH) is crucial for the apoptotic response upon serine starvation. Journal of Biological Chemistry, 290, 457–466.
- Pacold, M.E., Brimacombe, K.R., Chan, S.H., Rohde, J.M., Lewis, C.A., Swier, L.J., Possemato, R., Chen, W.W., Sullivan, L.B., Fiske, B.P., Cho, S., Freinkman, E., Birsoy, K., Abu-Remaileh, M., Shaul, Y.D., Liu, C.M., Zhou, M., Koh, M.J., Chung, H., Davidson, S.M., Luengo, A., Wang, A.Q., Xu, X., Yasgar, A., Liu, L., Rai, G., Westover, K.D., Vander Heiden, M.G., Shen, M., Gray, N.S., Boxer, M.B. & Sabatini, D.M. (2016) A PHGDH inhibitor reveals coordination of serine synthesis and one-carbon unit fate. Nature Chemical Biology, 12, 452–458.
- Palumbo, A. & Anderson, K. (2011) Multiple myeloma. New England Journal of Medicine, 364, 1046–1060.
- Pei, X.Y., Dai, Y. & Grant, S. (2004) Synergistic induction of oxidative injury and apoptosis in human multiple myeloma cells by the proteasome inhibitor bortezomib and histone deacetylase inhibitors. Clinical Cancer Research, 10, 3839–3852.
- Perez-Galan, P., Roue, G., Villamor, N., Montserrat, E., Campo, E. & Colomer, D. (2006) The proteasome inhibitor bortezomib induces apoptosis in mantle-cell lymphoma through generation of ROS and Noxa activation independent of p53 status. Blood, 107, 257–264.
- Polet, F., Corbet, C., Pinto, A., Rubio, L.I., Martherus, R., Bol, V., Drozak, X., Gregoire, V., Riant, O. & Feron, O. (2016) Reducing the serine availability complements the inhibition of the glutamine metabolism to block leukemia cell growth. Oncotarget, 7, 1765–1776.
- Pollari, S., Kakonen, S.M., Edgren, H., Wolf, M., Kohonen, P., Sara, H., Guise, T., Nees, M. & Kallioniemi, O. (2011) Enhanced serine production by bone metastatic breast cancer cells stimulates osteoclastogenesis. Breast Cancer Research and Treatment, 125, 421–430.
- Possemato, R., Marks, K.M., Shaul, Y.D., Pacold, M.E., Kim, D., Birsoy, K., Sethumadhavan, S., Woo, H.K., Jang, H.G., Jha, A.K., Chen, W.W., Barrett, F.G., Stransky, N., Tsun, Z.Y., Cowley, G.S., Barretina, J., Kalaany, N.Y., Hsu, P.P., Ottina, K., Chan, A.M., Yuan, B., Garraway, L.A., Root, D.E., Mino-Kenudson, M., Brachtel, E.F., Driggers, E.M. & Sabatini, D.M. (2011) Functional genomics reveal that the serine synthesis pathway is essential in breast cancer. Nature, 476, 346–350.
- Qin, Y., Zhang, S., Deng, S., An, G., Qin, X., Li, F., Xu, Y., Hao, M., Yang, Y., Zhou, W., Chang, H. & Qiu, L. (2017) Epigenetic silencing of miR-137 induces drug resistance and chromosomal instability by targeting AURKA in multiple myeloma. Leukemia, 31, 1123–1135.
- Raab, M.S., Podar, K., Breitkreutz, I., Richardson, P.G. & Anderson, K.C. (2009) Multiple myeloma. Lancet, 374, 324–339.
- Rodriguez, A.E., Ducker, G.S., Billingham, L.K., Martinez, C.A., Mainolfi, N., Suri, V., Friedman, A., Manfredi, M.G., Weinberg, S.E., Rabinowitz, J.D. & Chandel, N.S. (2019) Serine metabolism supports macrophage IL-1beta production. Cell Metabolism, 29, 1003–1011.e1004.
- Soriano, G.P., Besse, L., Li, N., Kraus, M., Besse, A., Meeuwenoord, N., Bader, J., Everts, B., den Dulk, H., Overkleeft, H.S., Florea, B.I. & Driessen, C. (2016) Proteasome inhibitor-adapted myeloma cells are largely independent from proteasome activity and show complex proteomic changes, in particular in redox and energy metabolism. Leukemia, 30, 2198–2207.
- Starheim, K.K., Holien, T., Misund, K., Johansson, I., Baranowska, K.A., Sponaas, A.M., Hella, H., Buene, G., Waage, A., Sundan, A. & Bjorkoy, G. (2016) Intracellular glutathione determines bortezomib cytotoxicity in multiple myeloma cells. Blood Cancer Journal, 6, e446.
- Tan, B., Qiu, Y., Zou, X., Chen, T., Xie, G., Cheng, Y., Dong, T., Zhao, L., Feng, B., Hu, X., Xu, L.X., Zhao, A., Zhang, M., Cai, G., Cai, S., Zhou, Z., Zheng, M., Zhang, Y. & Jia, W. (2013) Metabonomics identifies serum metabolite markers of colorectal cancer. Journal of Proteome Research, 12, 3000–3009.
- Vander Heiden, M.G., Cantley, L.C. & Thompson, C.B. (2009) Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science, 324, 1029–1033.
- Walsh, D.A. & Sallach, H.J. (1965) Purification and properties of chicken liver D-3-phosphoglycerate dehydrogenase. Biochemistry, 4, 1076–1085.
- Ward, P.S. & Thompson, C.B. (2012) Metabolic reprogramming: a cancer hallmark even warburg did not anticipate. Cancer Cell, 21, 297–308.
- Wu, M., Wanggou, S., Li, X., Liu, Q. & Xie, Y. (2017) Overexpression of mitochondrial serine hydroxyl-methyltransferase 2 is associated with poor prognosis and promotes cell proliferation and invasion in gliomas. OncoTargets and Therapy, 10, 3781–3788.
- Yin, L., Kufe, T., Avigan, D. & Kufe, D. (2014) Targeting MUC1-C is synergistic with bortezomib in downregulating TIGAR and inducing ROS-mediated myeloma cell death. Blood, 123, 2997–3006.
- Zaal, E.A., Wu, W., Jansen, G., Zweegman, S., Cloos, J. & Berkers, C.R. (2017) Bortezomib resistance in multiple myeloma is associated with increased serine synthesis. Cancer & Metabolism, 5, 7.
- Zeng, C., Wu, Q., Wang, J., Yao, B., Ma, L., Yang, Z., Li, J. & Liu, B. (2016) NOX4 supports glycolysis and promotes glutamine metabolism in non-small cell lung cancer cells. Free Radical Biology and Medicine, 101, 236–248.
- Zhang, L.L., Li, Y.Y., Hu, C.P. & Yang, H.P. (2014) Myelomatous pleural effusion as an initial sign of multiple myeloma-a case report and review of literature. Journal of Thoracic Disease, 6, E152–E159.
- Zhang, B., Zheng, A., Hydbring, P., Ambroise, G., Ouchida, A.T., Goiny, M., Vakifahmetoglu-Norberg, H. & Norberg, E. (2017) PHGDH defines a metabolic subtype in lung adenocarcinomas with poor prognosis. Cell Reports, 19, 2289–2303.
- Zhou, W., Yang, Y., Xia, J., Wang, H., Salama, M.E., Xiong, W., Xu, H., Shetty, S., Chen, T., Zeng, Z., Shi, L., Zangari, M., Miles, R., Bearss, D., Tricot, G. & Zhan, F. (2013) NEK2 induces drug resistance mainly through activation of efflux drug pumps and is associated with poor prognosis in myeloma and other cancers. Cancer Cell, 23, 48–62.
- Zhou, W., Yang, Y., Gu, Z., Wang, H., Xia, J., Wu, X., Zhan, X., Levasseur, D., Zhou, Y., Janz, S., Tricot, G., Shi, J. & Zhan, F. (2014) ALDH1 activity identifies tumor-initiating cells and links to chromosomal instability signatures in multiple myeloma. Leukemia, 28, 1155–1158.
Citing Literature
