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Serine Catabolism Regulates Mitochondrial Redox Control during Hypoxia
Open accessPublished version of a preprint
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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In the citing paper
“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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“SHMT2 expression has been found to be elevated in myc-transformed cells and human glioblastoma tumors and promotes cancer cell survival [64,65].”
BackgroundOne-carbon metabolism for cancer diagnostic and therapeutic approaches
Asai, A., Konno, M., Koseki, J., Taniguchi, M., Vecchione, A. M., & Ishii, H. (2019) · Cancer Letters · doi:10.1016/j.canlet.2019.11.023 · Cited by 42
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BackgroundThe Intersection of Serine Metabolism and Cellular Dysfunction in Retinal Degeneration
Sinha, T., Ikelle, L., Naash, M. I., & Al‐Ubaidi, M. R. (2020) · Cells · doi:10.3390/cells9030674 · Cited by 45
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One Carbon Metabolism and Mammalian Pregnancy Outcomes
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InfluentialMitochondrial Redox Metabolism: The Epicenter of Metabolism during Cancer Progression
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“Moreover, there is a positive correlation between mitochondrial serine catabolism and cytosolic de novo serine biosynthesis, indicating the contribution of the cytosolic serine biosynthesis pathway in maintaining redox metabolism in the mitochondria [135] (Figure 2).”
BackgroundActivation of the methylation cycle in cells reprogrammed into a stem cell-like state
Fernández‐Arroyo, S., Cuyàs, E., Bosch‐Barrera, J., Alarcón, T., Joven, J., & Menéndez, J. A. (2016) · Oncoscience · doi:10.18632/oncoscience.280 · Cited by 39
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Dong, Y., Yuan, Q., Ren, J., Li, H., Guo, H., Guan, H., Jiang, X., Qi, B., & Li, R. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1090906 · Cited by 38
“According to evidence, excessive ROS production results in oxidative stress in tissues and cells, which results in several disorders, including cancer (7, 8).”
InfluentialTarget enzymes in serine‐glycine‐one‐carbon metabolic pathway for cancer therapy
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“increased cellular ROS levels and induction of hypoxia-induced cell death in MYC-dependent cancer cells.(94) Furthermore, SHMT2 promotes liver regeneration by increasing the glycine levels and activating”
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“One pivotal enzyme in this puzzle may well be serine hydroxymethyltransferase (SHMT) which is critical in maintaining redox state of cells under oxidative stress (Mart ınez-Reyes and Chandel 2014), is responsive to the oxygen sensor HIF1-alpha (Ye et al. 2014; Semenza 2017) and a control point for the competitive dist…”
BackgroundInfluentialNon-coding RNAs rewire cancer metabolism networks
Lin, X., Wu, Z., Hu, H., Luo, M., & Song, E. (2021) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2020.12.019 · Cited by 37
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Targeting of chimeric antigen receptor T cell metabolism to improve therapeutic outcomes
Nanjireddy, P., Olejniczak, S. H., & Buxbaum, N. P. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1121565 · Cited by 39
“SHMT2 KD T cells could be rescued completely with the combination of formate, a product of mitochondrial one carbon metabolism, and N-acetyl cysteine (NAC), a glutathione precursor, reaffirming the important role of mitochondrial one-carbon metabolism in promoting T cell survival (50, 58, 59).”
BackgroundHigh tumor glycine concentration is an adverse prognostic factor in locally advanced rectal cancer
Redalen, K. R., Sitter, B., Bathen, T. F., Grøholt, K. K., Hole, K. H., Dueland, S., Flatmark, K., Ree, A. H., & Seierstad, T. (2015) · Radiotherapy and Oncology · doi:10.1016/j.radonc.2015.11.031 · Cited by 36
“A recent report demonstrated that the SHMT2 enzyme was induced by hypoxia and that its expression was correlated to both increased proliferation and unfavorable patient prognosis [18].”
BackgroundCell Proliferation in Neuroblastoma
Stafman, L. L., & Beierle, E. A. (2016) · Cancers · doi:10.3390/cancers8010013 · Cited by 36
PHGDH supports liver ceramide synthesis and sustains lipid homeostasis
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“…cell metabolism has been well studied (Diehl et al., 2019; Labuschagne et al., 2014; Maddocks et al., 2013; Maddocks et al., 2016; Maddocks et al., 2017; Pacold et al., 2016; Sullivan et al., 2019; Ye et al., 2014; Ye et al., 2012), less is known about the importance of PHGDH in normal tissues.”
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“Some studies have even reported that tumor cells required SHMT2 to support tumor growth by maintaining the redox balance and cell survival [12, 13].”
BackgroundSelf-citationMetabolic response to radiation therapy in cancer
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Hypoxic adaptation of mitochondria and its impact on tumor cell function
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“Interestingly, in myc-transformed cells, hypoxia induces expression of mitochondrial SHMT2 which reduces cytoplasmic oxidative stress and is protective, enhancing model tumor growth [83].”
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From the (Epi)Genome to Metabolism and Vice Versa; Examples from Hematologic Malignancy
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Serine hydroxymethyltransferase 2: a novel target for human cancer therapy
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“Although the oxidative pentose phosphate pathway produces the majority of NADPH 43,44 , SGOC metabolism has an important role in generating NADPH through methylene tetrahydrofolate dehydrogenase (MTHFD), the first enzyme downstream of SHMT, to manage oxidative stress 43,45,46 .”
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“…the mitochondrial isoform of SHMT (SHMT2) has been shown to be a crucial factor for the serine/glycine metabolism of several cancer cell types, 24–27 the expression pattern of SHMT2 and the correlation of expression level of SHMT2 and other clinicopathological parameters in clinical breast…”
SHMT2 Promotes Liver Regeneration Through Glycine-activated Akt/mTOR Pathway
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“ity of available vasculature to provide oxygen and nutrients to liver tissues.(15,31) Interestingly, parallel expression”
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SHMT2 Promotes Gastric Cancer Development through Regulation of HIF1α/VEGF/STAT3 Signaling
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“Studies have shown that SHMT2 can be co-induced by HIF1α and Myc in neuroblastoma tumors, and, in the absence of oxygen, SHMT2 maintains cell growth by balancing the NADPH/NADP+ ratios [34].”
BackgroundMetabolic reprogramming in nasopharyngeal carcinoma: Mechanisms and therapeutic opportunities
Liu, Q., Bode, A. M., Chen, X., & Luo, X. (2023) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2023.189023 · Cited by 28
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“24 Interestingly, the Warburg effect parallels the metabolic profile of activated NK cells that was described earlier.”
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“Previous research has demonstrated that reducing key enzymes like SHMT2 or MTHFD2 can decrease the NADPH/NADP + and GSH/GSSG ratios, increase cellular ROS levels, and induce cell death under stress conditions [13, 51].”
BackgroundThe Folate Cycle Enzyme MTHFR Is a Critical Regulator of Cell Response to MYC-Targeting Therapies
Su, A. H., Ling, F. W., Vaganay, C., Sodaro, G., Benaksas, C., Bello, R. D., Forget, A., Pardieu, B., Lin, K., Rutter, J. C., et al. (2020) · Cancer Discovery · doi:10.1158/2159-8290.cd-19-0970 · Cited by 29
“This is consistent with previous studies showing that MYC promotes expression of SHMT2, MTHFD2, and MTHFD1L mitochondrial enzymes which contribute to purine production through the THF salvage pathway (27, 28).”
Resultvan der Mijn, J. C., Chen, Q., Laursen, K. B., Khani, F., Wang, X., Dorsaint, P., Sboner, A., Gross, S. S., Nanus, D. M., & Gudas, L. J. (2022) · Molecular Carcinogenesis · doi:10.1002/mc.23437 · Cited by 27
“This increase in GSH may be linked to enhanced activity of the mitochondrial folate/one‐carbon pathway, extending findings to mice that had previously been shown only in cell culture experiments.(49,54,55) Importantly, the mitochondrial folate one‐carbon pathway functions as a source of one‐carbon units for high‐”
BackgroundSuccinate Anaplerosis Has an Onco-Driving Potential in Prostate Cancer Cells
Silva, A. C. B. S., Pérez-Valencia, J. A., Sciacovelli, M., Lalou, C., Sarlak, S., Tronci, L., Nikitopoulou, E., Mészáros, A., Frezza, C., Rossignol, R., et al. (2021) · Cancers · doi:10.3390/cancers13071727 · Cited by 28
“Recent studies have shown that cancer cells require SHMT (particularly SHMT2) for optimal proliferation and tumorigenicity, indicating the importance of serine catabolism in cancer [67,68].”
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“Moreover, HIF-1α was validated to be able to induce SHMT2 expression in hypoxic microenvironment [40].”
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“Between the only 2 SHMT members, expression of SHMT2 is significantly upregulated in a variety of cancers compared with SHMT1 [9,23].”
BackgroundInfluentialFolate Transport and One-Carbon Metabolism in Targeted Therapies of Epithelial Ovarian Cancer
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“In this regard, it was shown that serine supplementation decreased ROS damage in mice with oxidative stress through direct involvement in GSH synthesis [88]; the property of promoting glycolysis and GSH production is apparently unique to this amino acid [89].”
BackgroundCancer proteome and metabolite changes linked to SHMT2
Tong, J., Krieger, J. R., Taylor, P., Bagshaw, R., Kang, J., Jeedigunta, S., Wybenga-Groot, L. E., Zhang, W., Badr, H., Mirhadi, S., et al. (2020) · PLoS ONE · doi:10.1371/journal.pone.0237981 · Cited by 24
Glycyrrhetinic acid restricts mitochondrial energy metabolism by targeting SHMT2
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“In addition, SHMT2 is essential for maintaining redox balance and cell survival, and SHMT2 repression impairs antioxidant production and results in a significant increase in ROS under hypoxia, usually leading to cell death (Balsa et al., 2020; Yang et al., 2020; Ye et al., 2014).”
BackgroundZhou, Y., Wang, S., Wu, W., Jing, L., Li, H., Jia, Q., Zheng, J., Zheng, X., Yu, R., Wu, Q., et al. (2022) · EBioMedicine · doi:10.1016/j.ebiom.2022.104397 · Cited by 24
When cancer needs what's non-essential
Sullivan, M. R., & Heiden, M. G. V. (2017) · Nature Cell Biology · doi:10.1038/ncb3523 · Cited by 23
Transporters in vitamin uptake and cellular metabolism: impacts on health and disease
Yuan, Y., & Chen, L. (2025) · Life Metabolism · doi:10.1093/lifemeta/loaf008 · Cited by 25
“The folate cycle begins with the catalysis of serine by serine hydroxymethyltransferase (SHMT), converting serine to glycine and producing 5,10-methylenetetrahydrofolate (5,10-MTHF) to support de novo purine and thymidylate synthesis [184].”
Metabolic adaptations in cancer progression
Peng‐Winkler, Y., & Fendt, S. (2025) · Physiological Reviews · doi:10.1152/physrev.00037.2024 · Cited by 25
Stress-Mediated Reprogramming of Prostate Cancer One-Carbon Cycle Drives Disease Progression
Pällmann, N., Deng, K., Livgård, M., Tesikova, M., Jin, Y., Frengen, N. S., Kahraman, N., Mokhlis, H. A., Özpolat, B., Kildal, W., et al. (2021) · Cancer Research · doi:10.1158/0008-5472.can-20-3956 · Cited by 23
“Moreover, NADH production by the m1C cycle could contribute to prostate cancer development by enhancing the antioxidant defense of cancer cells (42, 43).”
BackgroundChen, X., Wang, Z., Wu, Y., Lan, Y., & Li, Y. (2023) · Frontiers in Oncology · doi:10.3389/fonc.2023.1204335 · Cited by 23
“The oncogenic transcription factor cMyc in tumor cells acts on serine hydroxymethyltransferase (SHMT) to promote tumor proliferation by depleting serine (10, 11).”
BackgroundXie, S.-Y., Shi, D., Ouyang, Y. Q., Cheng, X.-Y., Chen, X., Jiang, T., Xia, W., Guo, L., & Lin, H. (2021) · Research Square · doi:10.21203/rs.3.rs-1016628/v1 · Cited by 22
The mitochondrial gene-CMPK2 functions as a rheostat for macrophage homeostasis
Arumugam, P., Chauhan, M., Rajeev, T., Chakraborty, R., Bisht, K., Madan, M., Shankaran, D., Ramalingam, S., Gandotra, S., & Rao, V. A. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.935710 · Cited by 22
“Additionally, repression of serine catabolism by silencing SHMT2 in cancer cells has been shown to result in enhanced ROS under hypoxia (69).”
BackgroundPadinharayil, H., Rai, V., & George, A. (2023) · Cancers · doi:10.3390/cancers15041070 · Cited by 26
“In the latter case, NADPH synthesis (which is essential for lipogenesis and the maintenance of redox equilibrium) is maintained by serine catabolism through serine hydroxy methyltransferase 2 (SHMT2) using reducing equivalents [51,52].”
Epigenome–metabolism nexus in the retina: implications for aging and disease
Mondal, A. K., Gaur, M., Advani, J., & Swaroop, A. (2024) · Trends in Genetics · doi:10.1016/j.tig.2024.04.012 · Cited by 20
“Additionally, serine metabolism branching from glycolytic intermediates provides NADPH, which is crucial for maintaining cellular redox potential during phototransduction [57,58].”
SHMT2 promotes the tumorigenesis of renal cell carcinoma by regulating the m6A modification of PPAT
Huo, F., Xie, M., Zhu, Z., Zheng, J., & Pei, D. (2022) · Genomics · doi:10.1016/j.ygeno.2022.110424 · Cited by 21
Importance of lactate dehydrogenase (LDH) and monocarboxylate transporters (MCTs) in cancer cells
Hatami, H., Sajedi, A., Mir, S. M., & Memar, M. Y. (2022) · Health Science Reports · doi:10.1002/hsr2.996 · Cited by 21
“In hypoxia conditions, induced overexpression of mitochondrial SHMT2 (serine hydroxyl methyl transferase 2) protects cells against the toxic effects of oxidative stress.(42) The increase in lactate production in cancer cells has several effects on the other host tissue and cells.”
BackgroundExploiting the metabolic vulnerability of circulating tumour cells
Merteroglu, M., & Santoro, M. M. (2024) · Trends in cancer · doi:10.1016/j.trecan.2024.03.004 · Cited by 22
Sun, T., Song, C., Zhao, G., Feng, S., Wei, J., Zhang, L., Liu, X., Li, Z., & Zhang, H. (2023) · Cell Death and Disease · doi:10.1038/s41419-023-06335-5 · Cited by 20
“However, despite their high glycolytic rates, mitochondrial metabolism is necessary for cancer cell proliferation and tumorigenesis [28, 29].”
BackgroundEvaluating the clinical significance of SHMT2 and its co-expressed gene in human kidney cancer
Wang, H., Chong, T., Li, B.-Y., Chen, X.-S., & Zhen, W.-B. (2020) · Biological Research · doi:10.1186/s40659-020-00314-2 · Cited by 20
SHMT2 expression as a diagnostic and prognostic marker for thyroid cancer
Jin, M., Lee, W. K., You, M., Jang, A., Cheng, S.-Y., Kim, W. G., Jeon, M. J., & Lee, Y. (2021) · Endocrine Connections · doi:10.1530/ec-21-0135 · Cited by 19
Glenny, E. M., Coleman, M. F., Giles, E. D., Wellberg, E. A., & Hursting, S. D. (2021) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-120420-032437 · Cited by 18
Lacombe, V., Lenaers, G., & Urbanski, G. (2022) · Nutrients · doi:10.3390/nu14102058 · Cited by 21
“The importance of the one-carbon cycle in tumorigenesis and tumor growth also requires other enzymes and compounds related to this cycle, for promoting its functions [129,130].”
BackgroundLi, S., Han, H., Yang, K., Li, X., Ma, L., Yang, Z. R., & Zhao, Y. (2024) · International Immunopharmacology · doi:10.1016/j.intimp.2024.113702 · Cited by 21
Chakrabarti, G., Boothman, D. A., & Gerber, D. E. (2015) · Clinical Pharmacology Advances and Applications · doi:10.2147/cpaa.s79760 · Cited by 22
Glucometabolic reprogramming: From trigger to therapeutic target in hepatocellular carcinoma
Xia, H., Huang, Z., Wang, Z., Liu, S., Zhao, X., You, J., Xu, Y., Yam, J. W. P., & Cui, Y. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.953668 · Cited by 18
“Additionally, c-Mycregulated, serine hydroxymethyltransferase-2 (SHMT2)-dependent NADPH production is considered necessary for the maintenance of redox balance and survival of myc-transformed cells under hypoxic conditions (29).”
BackgroundSHMT2 Induces Stemness and Progression of Head and Neck Cancer
Jin, Y., Jung, S., Lim, M. A., Oh, C., Piao, Y., Kim, H. J., Nguyena, Q., Kang, Y. E., Chang, J. W., Won, H.-R., et al. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23179714 · Cited by 18
“proposed that MYC induces the transcriptional amplification of SHMT2, resulting in increased production of NADPH from NADP+, restrained cellular reactive oxygen species, and enhanced cancer cell survival [33].”
BackgroundNutrient metabolism of the nucleus pulposus: A literature review
Kodama, J., Wilkinson, K. J., & Otsuru, S. (2022) · North American Spine Society Journal (NASSJ) · doi:10.1016/j.xnsj.2022.100191 · Cited by 18
Anticancer therapeutic effect of ginsenosides through mediating reactive oxygen species
Li, X., Cao, D., Sun, S., & Wang, Y. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1215020 · Cited by 21
“…is activated to facilitate NADPH production and prevent anabolic processes that require NADPH depletion to optimize ROS yields, which significantly promotes the emergence of an aggressive phenotype (Aykin-Burns et al., 2009; Jeon et al., 2012; Ye et al., 2014; Vander Heiden and DeBerardinis, 2017).”
BackgroundThe central role of mitochondrial metabolism in hepatic steatosis
Win, S., Than, T. A., Kaplowitz, N., Wong, N., Arya, A., Win, Z. T., Win, S. H., Phyu, E., Kuemerle, C., Suh, J., et al. (2024) · Exploration of Digestive Diseases · doi:10.37349/edd.2024.00039 · Cited by 18
Meliton, A. Y., Shin, K. W. D., Çetin-Atalay, R., Atalay, V., Tian, Y., Szafran, J. C. H., Cho, T., Sun, K. A., Woods, P. S., Shamaa, O. R., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-64320-2 · Cited by 18
Clark, R. A., Qiao, J., Jacobson, J. C., & Chung, D. H. (2021) · Oncotarget · doi:10.18632/oncotarget.28168 · Cited by 17
“Although little is known about the exact role of SHMT2 in NB, a recent report found an association between SHMT2, N-Myc expression and high-risk NB [10].”
BackgroundResultInfluentialNayeen, M. J., Katinas, J. M., Magdum, T., Shah, K., Wong-Roushar, J., O’Connor, C. E., Fifer, A. N., Wallace-Povirk, A., Hou, Z., Matherly, L. H., et al. (2023) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.3c00763 · Cited by 17
Metabolism-Associated Epigenetic and Immunoepigenetic Reprogramming in Liver Cancer
Fan, C., Kam, S., & Ramadori, P. (2021) · Cancers · doi:10.3390/cancers13205250 · Cited by 17
“Furthermore, it is important to note that hypoxia in liver cancer might also have a strong impact in the regulation of many mitochondrial enzymes involved in one-carbon metabolism [57], therefore, contributing to sustain cell growth and survival.”
BackgroundHypoxia-induced one-carbon metabolic reprogramming in glioma stem-like cells
He, X., Wang, J., Shi, M.-Y., Liu, C., & Teng, Z. (2023) · Life Medicine · doi:10.1093/lifemedi/lnad048 · Cited by 16
Johnston, H., Dickinson, P., Ivens, A. C., Buck, A. H., Levine, R. D., Remacle, F., & Campbell, C. J. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1909455116 · Cited by 16
Tan, H., Hu, B., Liu, W., Liao, A., Wang, Y., He, W., Zhang, Y., Chen, G., Luo, K., Tao, M., et al. (2023) · Aquaculture · doi:10.1016/j.aquaculture.2023.739931 · Cited by 15
Wallace-Povirk, A., O’Connor, C. E., Dekhne, A. S., Bao, X., Nayeen, M. J., Schneider, M. J., Katinas, J. M., Wong-Roushar, J., Kim, S., Polin, L., et al. (2024) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-23-0550 · Cited by 15
He, J., Wang, A., Zhao, Q., Zou, Y., Zhang, Z., Sha, N., Hou, G., Zhou, B., Yang, Y. A., Chen, T., et al. (2024) · Nature Structural & Molecular Biology · doi:10.1038/s41594-024-01309-3 · Cited by 17
“5d), transcription of SHMT1 , SHMT2 and SFXN1 , genes relevant to serine carbon incorporation into folate cycle 32,33 , were decreased simultaneously, whereas the expression of SDS , which encodes the cytosolic enzyme L-serine dehydratase/deaminase 34–36 , was greatly promoted, implying that serine…”
Xing, R., Liu, R., Man, Y., Liu, C., Zhang, Y., Gao, H., & Yang, W. (2025) · Cell Discovery · doi:10.1038/s41421-024-00758-w · Cited by 16
Kong, W., Wang, Z., Chen, N., Mei, Y., Li, Y., & Yue, Y. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.914332 · Cited by 14
“Simultaneously, the synthesis of serine is essential for maintaining cell redox homeostasis (30).”
BackgroundHsieh, C.-H., Huang, C.-T., Cheng, Y., Hsu, C., Hsu, W., Chung, Y.-H., Liu, Y., Yang, T., Chien, C., Lee, Y., et al. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.115429 · Cited by 13
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“Moreover, previous studies showed that SHMT2 maintained a redox balance during hypoxia, and depletion of SHMT2 elevated the level of ROS, causing the death of cells under hypoxia [6].”
BackgroundIdentification of three new compounds that directly target human serine hydroxymethyltransferase 2
Han, Y., He, L., Qi, Y., Zhao, Y., Pan, Y., Fang, B., Li, S., Zhang, J. Z. H., & Zhang, L. (2020) · Chemical Biology & Drug Design · doi:10.1111/cbdd.13774 · Cited by 13
“, 2016), central nervous system (CNS), kidney, and bladder cancer (Jain et al., 2012; Lee et al., 2014; Ye et al., 2014).”
BackgroundSelf-citationImplementing Curcumin in Translational Oncology Research
Gall‐Tros̆elj, K., Samaržija, I., Tomljanović, M., Kujundžić, R. N., Đaković, N., & Mojzeš, A. (2020) · Molecules · doi:10.3390/molecules25225240 · Cited by 13
Du, J., Huang, Y., Jing, S., Pei, Y., Qian, Y., & Zeng, Y. (2022) · Translational Cancer Research · doi:10.21037/tcr-21-2485 · Cited by 12
“(19), SHMT2 was correlated to hypoxia-inducible factor-1α (HIF-1α) in myc-amplified neuroblastoma patient samples and contributed to the survival in an ischemia environment.”
Background
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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