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Serine Catabolism Regulates Mitochondrial Redox Control during Hypoxia
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Abstract
The de novo synthesis of the nonessential amino acid serine is often upregulated in cancer. In this study, we demonstrate that the serine catabolic enzyme, mitochondrial serine hydroxymethyltransferase (SHMT2), is induced when MYC-transformed cells are subjected to hypoxia. In mitochondria, SHMT2 can initiate the degradation of serine to CO2 and NH4+, resulting in net production of NADPH from NADP+. Knockdown of SHMT2 in MYC-dependent cells reduced cellular NADPH:NADP+ ratio, increased cellular reactive oxygen species, and triggered hypoxia-induced cell death. In vivo, SHMT2 suppression led to impaired tumor growth. In MYC-amplified neuroblastoma patient samples, there was a significant correlation between SHMT2 and hypoxia-inducible factor-1 α (HIF1α), and SHMT2 expression correlated with unfavorable patient prognosis. Together, these data demonstrate that mitochondrial serine catabolism supports tumor growth by maintaining mitochondrial redox balance and cell survival. Significance: In this study, we demonstrate that the mitochondrial enzyme SHMT2 is induced upon hypoxic stress and is critical for maintaining NADPH production and redox balance to support tumor cell survival and growth. Cancer Discov; 4(12); 1406–17. ©2014 AACR. See related commentary by Martínez-Reyes and Chandel, p. 1371 This article is highlighted in the In This Issue feature, p. 1355
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“SHMT2 is unlikely to directly demethylate trigonelline because it is not a N-methyltransferase and is known to cross-talk with NAD+ metabolism indirectly37,38.”
From Trigonelline Is an NAD+ Precursor That Improves Muscle Function during Ageing and Is Reduced in Human Sarcopenia (2024) · cites this paper as [37]
In the citing paper
“Loss of SHMT2 in hypoxic cells increases reactive oxygen species (ROS) levels, resulting in cell death.”
From Hypoxia signaling in cancer: Implications for therapeutic interventions (2023) · cites this paper as [61]
In the citing paper
“SHMT2 also plays a role in redox balance.”
From A review of small-molecule inhibitors of one-carbon enzymes: SHMT2 and MTHFD2 in the spotlight (2021) · cites this paper as [126]
In the citing paper
“Hypoxia induces SHMT2 expression and was found to be necessary for redox homeostasis and cell survival under hypoxic conditions.”
From A review of small-molecule inhibitors of one-carbon enzymes: SHMT2 and MTHFD2 in the spotlight (2021) · cites this paper as [126]
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BackgroundGLUT1 overexpression in CAR-T cells induces metabolic reprogramming and enhances potency
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Ciccarese, F., & Ciminale, V. (2017) · Frontiers in Oncology · doi:10.3389/fonc.2017.00117 · Cited by 104
“Serine catabolism in mitochondria produces glycine, essential for glutathione and purine synthesis, and contributes to mitochondrial redox balance in cancer cells exposed to hypoxia (106).”
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Serine signaling governs metabolic homeostasis and health
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Metabolic Plasticity of Tumor Cell Mitochondria
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“Indeed, MTHFD2 activity maintains a high NADPH:NADP ratio, and NADPH is required for regeneration of the antioxidant tripeptide glutathione and hence for protection from ROS damage (57).”
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“…results in a reduction in mitochondrial mass, O 2 consumption, and ROS generation (389); and (iii) hypoxia-induced HIF-1 increases the expression of the mitochondrial isoforms of SHMT1 and SHMT2, leading to increased mitochondrial NADPH and decreased mitoROS levels in Myc-transformed cells (380).”
Glutamine addiction in tumor cell: oncogene regulation and clinical treatment
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“SHMT2 catalyzes the conversion of serine to glycine plus a tetrahydrofolate-bound singlecarbon unit, which subsequently facilitates glutathione and nucleotide synthesis, mitochondrial NADPH generation, and mitochondrial redox balance during hypoxia (38).”
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“Accordingly, there is increasing focus on the role of 1CM in cancer metabolism and growth (47), which has revealed additional functions including mitochondrial NADPH production and redox control in hypoxia (48).”
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Pramono, A. A., Rather, G. M., Herman, H., Lestari, K., & Bertino, J. R. (2020) · Biomolecules · doi:10.3390/biom10030358 · Cited by 88
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“HIF was shown to induce the overexpression of SHMT2 [96] and PHGDH [97] to support serine metabolism-related NADPH synthesis, thereby maintaining mitochondrial redox homeostasis in hypoxia.”
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“On the other hand, serine catabolism through the mitochondrial 1C unit pathway is critical for maintaining cellular redox control under stress conditions (12, 13).”
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Farhadi, P., Yarani, R., Dokaneheifard, S., & Mansouri, K. (2020) · Tumor Biology · doi:10.1177/1010428320965284 · Cited by 86
“Also, it maintains redox homeostasis via the folate cycle.(116,117) 3-phosphoglycerate (3-PG), one of the glycolytic pathway metabolite, is the precursor of serine which is affected by the phosphoglycerate dehydrogenase (PHGDH).”
BackgroundSystems biology of oxygen homeostasis
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“Similarly, knockdown of SHMT2 in neuroblastoma cell lines increased oxidant stress and cell death under hypoxic conditions.(62) SHMT2 expression promoted survival of glioblastoma cells in the hypoxic tumor microenvironment.”
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Schito, L., & Rey, S. (2017) · Trends in Cell Biology · doi:10.1016/j.tcb.2017.10.006 · Cited by 83
Mechanisms of redox metabolism and cancer cell survival during extracellular matrix detachment
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“Additionally, whenMYCtransformed cells are exposed to hypoxic conditions, they require the activity of SHMT2 to break down serine and thus maintain NADPH production and redox balance necessary for tumor cell survival (56).”
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InfluentialPHGDH as a Key Enzyme for Serine Biosynthesis in HIF2α-Targeting Therapy for Renal Cell Carcinoma
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“Another example is that mitochondrial enzyme SHMT2 is induced upon hypoxia and is critical for maintaining NADPH production and redox balance to support cancer cell growth (Ye et al , 2014).”
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“Along with its anabolic function in nucleotide synthesis and protein translation, Ser catabolism in mitochondria is crucial to maintain NADPH production and redox balance [117].”
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“Under hypoxic stress, activated HIF1α enhances the expression of SHMT2 in an MYCdependent manner, which supports tumor growth by producing NADPH to counterbalance redox stress [121].”
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“Previous studies report that myc drives the up-regulation of the mitochondrial enzymes of one-carbon metabolism in hypoxia (47), however, c-myc levels have been shown to be significantly reduced in hypoxic HeLa cells (48).”
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“Indeed, PHGDH activity and the serine catabolic enzyme serine hydroxymethyltransferase (SHMT) activity are tightly correlated in transformed cells (13), and the strong correlation between the expression of PHGDH and the mitochondrial isoform SHMT2 in cancer suggests a particular wiring of metabolism in cancer cells th…”
BackgroundSelf-citationRole of Mitochondrial Stress Response in Cancer Progression
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“Additionally, serine catabolism via serine hydroxymethyltransferase 2 provides reducing equivalents to maintain NADPH/NADP balance [32], whereas increased serine synthesis by phosphoglycerate dehydrogenase leads to increased α-ketoglutarate levels that support anaplerotic flux for cancer growth [33].”
BackgroundEIF2A promotes cell survival during paclitaxel treatment in vitro and in vivo
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Serine and Metabolism Regulation: A Novel Mechanism in Antitumor Immunity and Senescence
Wu, Q., Chen, X., Li, J., & Sun, S. (2020) · Aging and Disease · doi:10.14336/ad.2020.0314 · Cited by 65
“DNA repair capacity and delay senescence in a progeroid mouse model [55].”
BackgroundRoles of Mitochondrial Serine Hydroxymethyltransferase 2 (SHMT2) in Human Carcinogenesis
Zeng, Y., Zhang, J., Xu, M., Chen, F., Zi, R., Yue, J., Zhang, Y., Chen, N., & Chin, Y. E. (2021) · Journal of Cancer · doi:10.7150/jca.60170 · Cited by 62
“Myc amplification was shown to promote upregulation of SHMT2 expression in a hypoxiainducible factor-1α (HIF-1α)-dependent manner, resulting in increased production of NADPH from NADP+, restrained cellular reactive oxygen species, and enhanced tumour cell survival [29].”
BackgroundSelf-citationMultiple mechanisms activate GCN2 eIF2 kinase in response to diverse stress conditions
Misra, J., Carlson, K. R., Spandau, D. F., & Wek, R. C. (2024) · Nucleic Acids Research · doi:10.1093/nar/gkae006 · Cited by 62
“The addition of cystine, glycine, and serine, which are used in the synthesis of glutathione ( 48 ,49 ), collectively yielded comparable results (Figure 6 F).”
ResultTargeting serine hydroxymethyltransferases 1 and 2 for T-cell acute lymphoblastic leukemia therapy
Pikman, Y., Ocasio-Martinez, N., Alexe, G., Dimitrov, B., Kitara, S., Diehl, F. F., Robichaud, A. L., Conway, A. S., Ross, L. S., Su, A. H., et al. (2021) · Leukemia · doi:10.1038/s41375-021-01361-8 · Cited by 59
“It stimulates expression of many nuclear encoded mitochondrial genes, regulates mitochondrial biogenesis [10], and is implicated in controlling the one-carbon folate pathway, especially in hypoxic conditions [11, 12].”
Cycling back to folate metabolism in cancer
Lee, Y., Vousden, K. H., & Hennequart, M. (2024) · Nature Cancer · doi:10.1038/s43018-024-00739-8 · Cited by 68
“This requirement can be met by increased 1C metabolism, for example, hypoxia due to insufficient blood supply leads to the upregulation of SHMT2, leading to the maintenance of NADPH production and redox balance in multiple cancer cell lines 72,99 .”
BackgroundOverview of Cancer Metabolism and Signaling Transduction
Chae, H., & Hong, S. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms24010012 · Cited by 66
“such as breast cancer and neuroblastoma [89].”
Cytosolic and mitochondrial NADPH fluxes are independently regulated
Niu, X., Stancliffe, E., Gelman, S. J., Wang, L., Schwaiger-Haber, M., Rowles, J. L., Shriver, L. P., & Patti, G. J. (2023) · Nature Chemical Biology · doi:10.1038/s41589-023-01283-9 · Cited by 59
Metabolic control of signalling pathways and metabolic auto‐regulation
Lorendeau, D., Christen, S., Rinaldi, G., & Fendt, S. (2015) · Biology of the Cell · doi:10.1111/boc.201500015 · Cited by 60
“Glycolysis and its connected pathways, such as the pentose phosphate pathway or the serine biosynthesis pathway can further provide energy (ATP via glycolysis), redox co-factors (NAD(P)+ / NAD(P)H via pentose phosphate pathway, pyruvate fermentation, or serine-folate metabolism (Lewis et al. 2014; Ye et al. 2014)), an…”
BackgroundMitochondrial Redox Hubs as Promising Targets for Anticancer Therapy
Ippolito, L., Giannoni, E., Chiarugi, P., & Parri, M. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.00256 · Cited by 60
“Indeed, mitochondrial serine hydroxymethyltransferase (SHMT2) is induced in hypoxic conditions and its activity results in a high NAPDH-dependent mROS balance, as the methyl donor methylene-tetrahydrofolate can be oxidized through the folate metabolic enzymes to generate NADPH, which is important for maintaining cellu…”
BackgroundDekhne, A. S., Shah, K., Ducker, G. S., Katinas, J. M., Wong-Roushar, J., Nayeen, M. J., Doshi, A., Ning, C., Bao, X., Frühauf, J., et al. (2019) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-19-0037 · Cited by 59
“SHMT2 is induced by hypoxic stress in Myc-transformed cells (21) and is critical to tumor cell survival in the hypoxic, nutrient-poor tumor microenvironment (17, 21).”
BackgroundSelf-citationA review of small-molecule inhibitors of one-carbon enzymes: SHMT2 and MTHFD2 in the spotlight
Cuthbertson, C. R., Arabzada, Z., Bankhead, A., Kyani, A., & Neamati, N. (2021) · ACS Pharmacology & Translational Science · doi:10.1021/acsptsci.0c00223 · Cited by 57
EWS/FLI is a Master Regulator of Metabolic Reprogramming in Ewing Sarcoma
Tanner, J. M., Bensard, C., Wei, P., Krah, N. M., Schell, J. C., Gardiner, J. D., Schiffman, J. D., Lessnick, S. L., & Rutter, J. P. (2017) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-17-0182 · Cited by 61
“Indeed, serine metabolism has been shown to be activated under conditions of increased ROS production, perhaps contributing to increased capacity to confront redox stress (51).”
BackgroundGuiducci, G., Paone, A., Tramonti, A., Giardina, G., Rinaldo, S., Bouzidi, A., Magnifico, M. C., Marani, M., Menéndez, J. A., Fatica, A., et al. (2019) · Nucleic Acids Research · doi:10.1093/nar/gkz129 · Cited by 56
“SHMT was already known to be controlled at both transcriptional (50) and post-translational level (51) and a cross-talk between SHMT1 and SHMT2 expression has also been reported (5,13).”
BackgroundInhibiting both proline biosynthesis and lipogenesis synergistically suppresses tumor growth
Liu, M., Wang, Y., Yang, C., Ruan, Y., Bai, C., Chu, Q., Cui, Y., Chen, C., Ying, G., & Li, B. (2020) · The Journal of Experimental Medicine · doi:10.1084/jem.20191226 · Cited by 57
“, 2011), and serine/one carbon metabolism (Fan et al., 2014; Lewis et al., 2014; Ye et al., 2014).”
The emerging roles of TRIM21 in coordinating cancer metabolism, immunity and cancer treatment
Chen, X., Cao, M., Wang, P., Chu, S., Li, M., Hou, P., Zheng, J., Li, Z., & Bai, J. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.968755 · Cited by 52
“Serine hydroxymethyltransferase 2 (SHMT2), which regulates the conversion of serine and glycine in mitochondria, is important for cell proliferation (50).”
BackgroundFerroptosis and its role in skeletal muscle diseases
Wang, Y., Zhang, Z., Jiao, W., Wang, Y., Wang, X., Zhao, Y., Fan, X., Tian, L., Li, X., & Mi, J. (2022) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2022.1051866 · Cited by 62
“In addition, despite no relevant research report that arginine, serine and glycine participate in the regulation of ferroptosis, the three amino acids have shown the potential to fight ferroptosis in some studies (Possemato et al., 2011; Ye et al., 2014; Sen et al., 2018), which needs more exploration and excavation.”
BackgroundHamanaka, R. B., & Mutlu, G. M. (2021) · Amino Acids · doi:10.1007/s00726-021-02996-8 · Cited by 54
“Cells lacking SHMT2 are characterized by increased levels of oxidized glutathione, oxidative stress, and increased sensitivity to oxidative stressors (Ye et al. 2014).”
BackgroundAmino acid metabolism in skeletal cells
Devignes, C.-S., Carmeliet, G., & Stegen, S. (2022) · Bone Reports · doi:10.1016/j.bonr.2022.101620 · Cited by 55
“others, to the generation of NADPH, which converts glutathione back to its reduced form and is critical for redox regulation under hypoxic conditions (Lieu et al., 2020; Ye et al., 2014).”
BackgroundShedding New Light on Cancer Metabolism: A Metabolic Tightrope Between Life and Death
Läsche, M., Emons, G., & Gründker, C. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.00409 · Cited by 55
“Anti-oxidative, reducing equivalents are delivered through glycolysis and reductive glutamine carboxylation [(76, 92, 93); Figures 2D,I].”
BackgroundMethodShmt2: A Stat3 Signaling New Player in Prostate Cancer Energy Metabolism
Marrocco, I., Fabio Altieri, F., Rubini, E., Paglia, G., Chichiarelli, S., Giamogante, F., Macone, A., Perugia, G., Magliocca, F. M., Gurtner, A., et al. (2019) · Cells · doi:10.3390/cells8091048 · Cited by 51
Yang, Y., Liu, S., Gao, H., Wang, P., Zhang, Y., Zhang, A., Jia, Z., & Huang, S. (2020) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2020.01.182 · Cited by 53
3-Phosphoglycerate dehydrogenase: a potential target for cancer treatment
Li, M., Wu, C., Yang, Y., Zheng, M., Yu, S., Wang, J., Chen, L., & Li, H. (2021) · Cellular Oncology · doi:10.1007/s13402-021-00599-9 · Cited by 51
He, L., Endress, J. E., Cho, S., Li, Z., Zheng, Y., Asara, J. M., & Blenis, J. (2022) · Science Advances · doi:10.1126/sciadv.abm8786 · Cited by 47
From direct to indirect lithium targets: a comprehensive review of omics data
Roux-Rouquié, M., & Dosseto, A. (2017) · Metallomics · doi:10.1039/c7mt00203c · Cited by 50
Zhang, Y., Liu, Z., Wang, X., Jian, H., Xiao, H., & Wen, T. (2022) · Cancer Gene Therapy · doi:10.1038/s41417-022-00470-5 · Cited by 47
“Knockdown of SHMT2 or inhibition of its activity by acetylation modification reduced the cellular NADPH/NADP ratio and increased ROS [30, 43], suggesting that SHMT2 suppression disrupts cellular redox homeostasis.”
BackgroundMethodSelf-citationLinking Serine/Glycine Metabolism to Radiotherapy Resistance
Sánchez‐Castillo, A., Vooijs, M., & Kampen, K. R. (2021) · Cancers · doi:10.3390/cancers13061191 · Cited by 47
“In MYC-amplified neuroblastomas, the correlation between SHMT2 and HIF1α was associated with poor patient prognosis, confirming the essential role of HIF1-induced SHMT2 regulation in maintaining therapy-resistant hypoxic cell survival [115].”
BackgroundWu, X., Deng, L., Tang, D., Ying, G., Yao, X., Liu, F., & Gui, L. (2015) · Tumor Biology · doi:10.1007/s13277-015-4506-8 · Cited by 47
“[18] that elevated expression of SHMT2 was shown to be associated with poor prognosis in human cancer, supporting the important role of SHMT2 in the control of cell proliferation in several cancer types [19, 20] and as a hot target for anticancer therapy.”
BackgroundSHMT2 Overexpression Predicts Poor Prognosis in Intrahepatic Cholangiocarcinoma
Ning, S., Ma, S., Saleh, A. Q., Guo, L., Zhao, Z., & Chen, Y. (2018) · Gastroenterology Research and Practice · doi:10.1155/2018/4369253 · Cited by 47
“Clinical data demonstrates that elevated expression of SHMT2 was shown to be independently associated with PFS and RFS [21, 22].”
Lee, S. E., Park, S., Yi, S., Choi, N. R., Lim, M. A., Chang, J. W., Won, H.-R., Kim, J. R., Ko, H. M., Chung, E., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-45366-0 · Cited by 46
Ser, Z., Gao, X., Johnson, C., Mehrmohamadi, M., Liu, X., Li, S., & Locasale, J. W. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.05.035 · Cited by 46
Zhang, L., Chen, Z., Xue, D., Zhang, Q., Liu, X., Luh, F., Hong, L., Zhang, H., Pan, F., Liu, Y., et al. (2016) · Oncology Reports · doi:10.3892/or.2016.5112 · Cited by 46
“Moreover, elevated expression of SHMT2 has been found to be associated with poor prognosis in human cancers (8).”
BackgroundMitonuclear Interactions Mediate Transcriptional Responses to Hypoxia inDrosophila
Mossman, J. A., Tross, J. G., Jourjine, N. A., Li, N., Wu, Z. J., & Rand, D. M. (2016) · Molecular Biology and Evolution · doi:10.1093/molbev/msw246 · Cited by 50
“Serine catabolism has been linked with tumor growth and mitochondrial redox balance during severe hypoxia (Ye et al. 2014), thus integrating both mitochondrial function and oxygen availability; two main objectives of the present study.”
BackgroundNADH Ties One-Carbon Metabolism to Cellular Respiration
Maynard, A. G., & Kanarek, N. (2020) · Cell Metabolism · doi:10.1016/j.cmet.2020.03.012 · Cited by 44
PHGDH as a mechanism for resistance in metabolically-driven cancers
Rathore, R., Schutt, C. R., & Tine, B. A. V. (2020) · Cancer Drug Resistance · doi:10.20517/cdr.2020.46 · Cited by 47
“Increased SHMT1/2 expression can drive serine catabolism, increasing mitochondrial NADH production and fuelling the NAD+ salvage pathway required for PHGDH activity and serine biosynthesis[59,77].”
BackgroundResearch into cancer metabolomics: Towards a clinical metamorphosis
Olivares, O., Däbritz, J. H. M., King, A., Gottlieb, E., & Halsey, C. (2015) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2015.09.008 · Cited by 45
“Elevated SHMT2 expression has also been linked to an adverse patient outcome in neuroblastoma, NSCLC and breast cancer [87-89].”
BackgroundNutrients in Energy and One-Carbon Metabolism: Learning from Metformin Users
Luciano‐Mateo, F., Hernández‐Aguilera, A., Cabré, N., Camps, J., Fernández‐Arroyo, S., López‐Miranda, J., Menéndez, J. A., & Joven, J. (2017) · Nutrients · doi:10.3390/nu9020121 · Cited by 44
Badur, M. G., & Metallo, C. M. (2017) · Metabolic Engineering · doi:10.1016/j.ymben.2017.11.013 · Cited by 44
“Several studies have also connected these pathways to cancer through hypoxia and “stemness” (Nilsson et al., 2014; Samanta et al., 2016; Ye et al., 2014), highlighting the need to study flux through this pathway in various microenvironments and biological contexts.”
BackgroundMYC Oncogene: A Druggable Target for Treating Cancers with Natural Products
Chan, K. I., Zhang, S., Li, G., Xu, Y., Cui, L., Wang, Y., Su, H., Tan, W., & Zhong, Z. (2024) · Aging and Disease · doi:10.14336/ad.2023.0520 · Cited by 46
Loss of PYCR2 Causes Neurodegeneration by Increasing Cerebral Glycine Levels via SHMT2
Escande‐Beillard, N., Loh, A., Saleem, S. N., Kanata, K., Hashimoto, Y., Altunoğlu, U., Metoska, A., Grandjean, J., Ng, F. M., Pomp, O., et al. (2020) · Neuron · doi:10.1016/j.neuron.2020.03.028 · Cited by 44
Metadata
- Authors
- Ye, J., Fan, J., Venneti, S., Wan, Y.-W., Pawel, B. R., Zhang, J., Finley, L. W. S., Lu, C., Lindsten, T., Cross, J. R., Qing, G., Liu, Z., Simon, M. C., Rabinowitz, J. D., & Thompson, C. B.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- Princeton University (US)
- Baylor College of Medicine (US)
- Children's Hospital of Philadelphia (US)
- 1Cancer Biology and Genetics Program and Immunology Program, Memorial Sloan Kettering Cancer Center, New York, New York.
- Huazhong University of Science and Technology (CN)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Thompson, Craig B.
- ORCID
- Venue
- Cancer Discovery
- Published
- 2014-12-01
- Volume
- 4
- Issue
- 12
- Pages
- 1406-1417
- ISSN
- 2159-8274 (ISSN-L)
- 2159-8290
- PMC
- PMC4258153
- OpenAlex
- W2163404652
- Cited by
- 452
- References
- 50
- Citations by year
- 2026: 31 · 2025: 29 · 2024: 40 · 2023: 38 · 2022: 46 · 2021: 58 · 2020: 67 · 2019: 36 · 2018: 21 · 2017: 27 · 2016: 34 · 2015: 19 · 2014: 5
- FWCI
- 9.08
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Cancer Discovery (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- Memorial Sloan-Kettering Cancer Center
- National Institutes of Health
- National Cancer Institute (K08CA181475, P01CA104838, K99CA184239, R01CA105463, P30CA008748, R01CA163591)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer and biochemical research
- Keywords
- serine catabolism, SHMT2, hypoxia, mitochondrial redox balance, NADPH/NADP+ ratio, reactive oxygen species, c-Myc, tumor growth, neuroblastoma, hypoxia-inducible factor-1α, hypoxia-induced cell death, cancer metabolism
- MeSH terms
- Animals, Hypoxia, Base Sequence, Cell Survival, Disease Models, Animal, Gene Amplification, Homeostasis, Humans, Mitochondria, Models, Biological, Molecular Sequence Data, Neoplasms, Oxidation-Reduction, Promoter Regions, Genetic, Serine, Glycine Hydroxymethyltransferase, Gene Expression, Genes, myc, Reactive Oxygen Species, Cell Line, Tumor, Tumor Burden, Phosphoglycerate Dehydrogenase, Mice, Hypoxia-Inducible Factor 1, alpha Subunit, Gene Knockdown Techniques, Heterografts
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