SHMT2 promotes cell viability and inhibits ROS-dependent, mitochondrial-mediated apoptosis via the intrinsic signaling pathway in bladder cancer cells
Open accessAbstract
Mitochondrial serine hydroxymethyltransferase (SHMT2) catalyzes the conversion of serine to glycine and concomitantly produces one-carbon units to support cell growth and is upregulated in various cancer cells. SHMT2 knockdown triggers cell apoptosis; however, the detailed mechanism of apoptosis induced by SHMT2 inactivation remains unknown. Here, we demonstrate that SHMT2 supports the proliferation of bladder cancer (BC) cells by maintaining redox homeostasis. SHMT2 knockout decreased the pools of purine and one-carbon units and delayed cell cycle progression in a manner that was rescued by formate, demonstrating that SHMT2-mediated one-carbon units are essential for BC cell proliferation. SHMT2 deficiency promoted the accumulation of intracellular reactive oxygen species (ROS) by decreasing the NADH/NAD + , NADPH/NADP + , and GSH/GSSG ratios, leading to a loss in mitochondrial membrane potential, release of cytochrome c , translocation of Bcl-2 family protein and activation of caspase-3. Notably, blocking ROS production with the one-carbon donor formate and the ROS scavenger N-acetyl-cysteine (NAC) effectively rescued SHMT2 deficiency-induced cell apoptosis via the intrinsic signaling pathway. Treatment with the SHMT inhibitor SHIN1 resulted in a significant inhibitory effect on cell proliferation and induced cell apoptosis. Formate and NAC rescued SHIN1-induced cell apoptosis. Our findings reveal an important mechanism by which the loss of SHMT2 triggers ROS-dependent, mitochondrial-mediated apoptosis, which gives insight into the link between serine metabolism and cell apoptosis and provides a promising target for BC treatment and drug discovery.
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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 indirectly.
“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 [38]
Cites
Genome engineering using the CRISPR-Cas9 system
Ran, F. A., Hsu, P. D., Wright, J., Agarwala, V., Scott, D. A., & Zhang, F. (2013) · Nature Protocols · doi:10.1038/nprot.2013.143 · Cited by 11,133 · see citing works
Oxidative stress: the mitochondria-dependent and mitochondria-independent pathways of apoptosis
Sinha, K., Das, J., Pal, P. B., & Sil, P. C. (2013) · Archives of Toxicology · doi:10.1007/s00204-013-1034-4 · Cited by 1,622 · see citing works
Metabolite profiling identifies a key role for glycine in rapid cancer cell proliferation
Jain, M., Nilsson, R., Sharma, S., Madhusudhan, N., Kitami, T., Souza, A. L., Kafri, R., Kirschner, M. W., Clish, C. B., & Mootha, V. K. (2012) · Science · doi:10.1126/science.1218595 · Cited by 1,403 · see citing works
Phosphoglycerate dehydrogenase diverts glycolytic flux and contributes to oncogenesis
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., et al. (2011) · Nature Genetics · doi:10.1038/ng.890 · Cited by 1,120 · see citing works
Reprogramming of glucose, fatty acid and amino acid metabolism for cancer progression
Li, Z., & Zhang, H. (2015) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-015-2070-4 · Cited by 829 · see citing works
Major apoptotic mechanisms and genes involved in apoptosis
Kiraz, Y., Adan, A., Yandım, M. K., & Baran, Y. (2016) · Tumor Biology · doi:10.1007/s13277-016-5035-9 · Cited by 585 · see citing works
Serine, but not glycine, supports one-carbon metabolism and proliferation of cancer cells
Labuschagne, C. F., van den Broek, N. J. F., Mackay, G. M., Vousden, K. H., & Maddocks, O. D. K. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.04.045 · Cited by 576 · see citing works
A PHGDH inhibitor reveals coordination of serine synthesis and one-carbon unit fate
Pacold, M. E., Brimacombe, K. R., Chan, S. H., Rohde, J. M., Lewis, C. A., Swier, L. J. Y. M., Possemato, R., Chen, W. W., Sullivan, L. B., Fiske, B. P., et al. (2016) · Nature Chemical Biology · doi:10.1038/nchembio.2070 · Cited by 553 · see citing works
One-carbon metabolism in cancer
Newman, A. C., & Maddocks, O. D. K. (2017) · British Journal of Cancer · doi:10.1038/bjc.2017.118 · Cited by 511 · see citing works
New aspects of amino acid metabolism in cancer
Vettore, L. A., Westbrook, R. L., & Tennant, D. A. (2019) · British Journal of Cancer · doi:10.1038/s41416-019-0620-5 · Cited by 503 · see citing works
Serine Catabolism Regulates Mitochondrial Redox Control during Hypoxia
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., et al. (2014) · Cancer Discovery · doi:10.1158/2159-8290.cd-14-0250 · Cited by 452 · see citing works
Self-citationAspartate is a limiting metabolite for cancer cell proliferation under hypoxia and in tumours
Garcia-Bermudez, J., Baudrier, L., La, K., Zhu, X. G., Fidelin, J., Sviderskiy, V. O., Papagiannakopoulos, T., Molina, H., Snuderl, M., Lewis, C. A., et al. (2018) · Nature Cell Biology · doi:10.1038/s41556-018-0118-z · Cited by 442 · see citing works
Maddocks, O. D. K., Labuschagne, C. F., Adams, P. D., & Vousden, K. H. (2016) · Molecular Cell · doi:10.1016/j.molcel.2015.12.014 · Cited by 440 · see citing works
Elia, I., Broekaert, D., Christen, S., Boon, R., Radaelli, E., Orth, M. F., Verfaillie, C. M., Grünewald, T. G. P., & Fendt, S. (2017) · Nature Communications · doi:10.1038/ncomms15267 · Cited by 426 · see citing works
Reversal of cytosolic one-carbon flux compensates for loss of the mitochondrial folate pathway
Ducker, G. S., Chen, L., Morscher, R. J., Ghergurovich, J. M., Esposito, M., Teng, X., Kang, Y., & Rabinowitz, J. D. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.04.016 · Cited by 419 · see citing works
SHMT2 drives glioma cell survival in ischaemia but imposes a dependence on glycine clearance
Kim, D., Fiske, B. P., Birsoy, K., Freinkman, E., Kami, K., Possemato, R. L., Chudnovsky, Y., Pacold, M. E., Chen, W. W., Cantor, J. R., et al. (2015) · Nature · doi:10.1038/nature14363 · Cited by 368 · see citing works
Metabolic reprogramming for cancer cells and their microenvironment: Beyond the Warburg Effect
Sun, L., Suo, C., Li, S., Zhang, H., & Gao, P. (2018) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2018.06.005 · Cited by 366 · see citing works
Metabolic phenotype of bladder cancer
Massari, F., Ciccarese, C., Santoni, M., Iacovelli, R., Roberta Mazzucchelli, A., Piva, F., Scarpelli, M., Berardi, R., Tortora, G., Antonio Lopez-beltran, B., et al. (2016) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2016.03.005 · Cited by 337 · see citing works
Mullarky, E., Lucki, N. C., Beheshti Zavareh, R., Anglin, J. L., Gomes, A. P., Nicolay, B. N., Wong, J. C. Y., Christen, S., Takahashi, H., Singh, P. K., et al. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1521548113 · Cited by 333 · see citing works
Sun, L., Song, L., Wan, Q., Wu, G., Li, X., Wang, Y., Wang, J., Liu, Z., Zhong, X., He, X., et al. (2015) · Cell Research · doi:10.1038/cr.2015.33 · Cited by 311 · see citing works
Self-citationAnalysis of the composition, assembly kinetics and activity of native Apaf‐1 apoptosomes
Hill, M. M. C., Adrain, C., Duriez, P. J., Creagh, E. M., & Martin, S. J. (2004) · The EMBO Journal · doi:10.1038/sj.emboj.7600210 · Cited by 299 · see citing works
Mitochondrial translation requires folate-dependent tRNA methylation
Morscher, R. J., Ducker, G. S., Li, H., Mayer, J., Gitai, Z., Sperl, W., & Rabinowitz, J. D. (2018) · Nature · doi:10.1038/nature25460 · Cited by 278 · see citing works
Enhanced serine production by bone metastatic breast cancer cells stimulates osteoclastogenesis
Pollari, S., Käkönen, S.-M., Edgren, H., Wolf, M., Kohonen, P., Sara, H., Guise, T., Nees, M., & Kallioniemi, O. (2011) · Breast Cancer Research and Treatment · doi:10.1007/s10549-010-0848-5 · Cited by 269 · see citing works
Ducker, G. S., Ghergurovich, J. M., Mainolfi, N., Suri, V., Jeong, S. K., Hsin-Jung Li, S., Friedman, A., Manfredi, M. G., Gitai, Z., Kim, H., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1706617114 · Cited by 261 · see citing works
Li, D., Ueta, E., Kimura, T., Yamamoto, T., & Osaki, T. (2004) · Cancer Science · doi:10.1111/j.1349-7006.2004.tb03323.x · Cited by 255 · see citing works
Oxidative stress-induced apoptosis in granulosa cells involves JNK, p53 and Puma
Yang, H., Xie, Y., Yang, D., & Ren, D. (2017) · Oncotarget · doi:10.18632/oncotarget.15813 · Cited by 232 · see citing works
SHMT2 Desuccinylation by SIRT5 Drives Cancer Cell Proliferation
Yang, X. P., Wang, Z., Li, X., Liu, B., Liu, M., Liu, L., Chen, S., Ren, M., Wang, Y., Yu, M., et al. (2017) · Cancer Research · doi:10.1158/0008-5472.can-17-1912 · Cited by 231 · see citing works
Serine Catabolism Feeds NADH when Respiration Is Impaired
Yang, L., García‐Cañaveras, J. C., Chen, Z., Wang, L., Liang, L., Jang, C., Mayr, J. A., Zhang, Z., Ghergurovich, J. M., Zhan, L., et al. (2020) · Cell Metabolism · doi:10.1016/j.cmet.2020.02.017 · Cited by 213 · see citing works
Nikiforov, M. A., Chandriani, S. J., O’Connell, B. C., Petrenko, O., Kotenko, I., Beavis, A. J., Sedivy, J. M., & Cole, M. D. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.16.5793-5800.2002 · Cited by 201 · see citing works
Minton, D. R., Nam, M., McLaughlin, D. J., Shin, J., Bayraktar, E. C., Alvarez, S., Sviderskiy, V. O., Papagiannakopoulos, T. Y., Sabatini, D. M., Birsoy, K., et al. (2018) · Molecular Cell · doi:10.1016/j.molcel.2018.01.024 · Cited by 192 · see citing works
Deacetylation of serine hydroxymethyl-transferase 2 by SIRT3 promotes colorectal carcinogenesis
Wei, Z., Song, J., Wang, G., Cui, X., Zheng, J., Tang, Y., Chen, X., Li, J., Cui, L., Liu, C., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-06812-y · Cited by 188 · see citing works
Garrow, T. A., Brenner, A., Whitehead, V. M., Chen, X. N., Duncan, R., Korenberg, J. R., & Shane, B. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)50286-1 · Cited by 179 · see citing works
RENWICK, S. B., Snell, K., & Baumann, U. (1998) · Structure · doi:10.1016/s0969-2126(98)00112-9 · Cited by 178 · see citing works
Serine and Functional Metabolites in Cancer
Newman, A. C., & Maddocks, O. D. K. (2017) · Trends in Cell Biology · doi:10.1016/j.tcb.2017.05.001 · Cited by 166 · see citing works
Comparative Oncogenomics Identifies PSMB4 and SHMT2 as Potential Cancer Driver Genes
Lee, G. Y., Haverty, P. M., Li, L., Kljavin, N. M., Bourgon, R., Lee, J., Stern, H. M., Modrusan, Z. D., Seshagiri, S., Zhang, Z., et al. (2014) · Cancer Research · doi:10.1158/0008-5472.can-13-2683 · Cited by 161 · see citing works
Wang, Q., Liberti, M. V., Liu, P., Deng, X., Liu, Y., Locasale, J. W., & Lai, L. (2017) · Cell Chemical Biology · doi:10.1016/j.chembiol.2016.11.013 · Cited by 147 · see citing works
Stover, P., & Schirch, V. (1990) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)77290-6 · Cited by 139 · see citing works
SHMT1 knockdown induces apoptosis in lung cancer cells by causing uracil misincorporation
Paone, A., Marani, M., Fiascarelli, A., Rinaldo, S., Giardina, G., Contestabile, R., Paiardini, A., & Cutruzzolà, F. (2014) · Cell Death and Disease · doi:10.1038/cddis.2014.482 · Cited by 129 · see citing works
The Bcl-2 gene family and apoptosis
Bruckheimer, E. M., Cho, S. H., Sarkiss, M. G., Herrmann, J. L., & McDonnell, T. J. (1998) · Advances in biochemical engineering, biotechnology · doi:10.1007/bfb0102306 · Cited by 123 · see citing works
Li, L., Wei, Y., To, C., Zhu, C., Tong, J., Pham, N., Taylor, P. P., Ignatchenko, V., Ignatchenko, A., Zhang, W., et al. (2014) · Nature Communications · doi:10.1038/ncomms6469 · Cited by 115 · see citing works
Amino acid management in cancer
Tsun, Z.-Y., & Possemato, R. (2015) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2015.08.002 · Cited by 113 · see citing works
PSAT1 regulates cyclin D1 degradation and sustains proliferation of non‐small cell lung cancer cells
Yang, Y., Wu, J., Cai, J., He, Z., Yuan, J. X., Zhu, X., Li, Y., Li, M., & Guan, H. (2014) · International Journal of Cancer · doi:10.1002/ijc.29150 · Cited by 107 · see citing works
Regulation of apoptosis by Bcl-2 cysteine oxidation in human lung epithelial cells
Luanpitpong, S., Chanvorachote, P., Stehlik, C., Tse, W., Callery, P. S., Wang, L., & Rojanasakul, Y. (2013) · Molecular Biology of the Cell · doi:10.1091/mbc.e12-10-0747 · Cited by 102 · see citing works
Reversal of Cytosolic One-Carbon Flux Compensates for Loss of the Mitochondrial Folate Pathway
Ducker, G. S., Chen, L., Morscher, R. J., Ghergurovich, J. M., Esposito, M., Teng, X., Kang, Y., & Rabinowitz, J. D. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.09.011 · Cited by 91 · see citing works
Nilsson, L. M., Plym Forshell, T. Z., Rimpi, S., Kreutzer, C., Pretsch, W., Bornkamm, G. W., & Nilsson, J. A. (2012) · PLoS Genetics · doi:10.1371/journal.pgen.1002573 · Cited by 85 · see citing works
Woo, C. C., Chen, W. C., Teo, X. Q., Radda, G. K., & Lee, P. T. H. (2016) · Oncotarget · doi:10.18632/oncotarget.10415 · Cited by 82 · see citing works
Su, C., Hsieh, K.-L., Wang, S.-C., Yeh, H., Huang, S., Liu, P., Fang, S.-H., Cheng, W.-C., Huang, K.-H., Chiu, F., et al. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20071647 · Cited by 70 · see citing works
Zhang, J., Wei, H., Liu, X., Wang, N., Qi, Y., Zhang, Y., & Shulan, Z. (2015) · Cancer Biology & Therapy · doi:10.1080/15384047.2015.1017690 · Cited by 61 · see citing works
Self-citationMarani, M., Paone, A., Fiascarelli, A., Macone, A., Gargano, M., Rinaldo, S., Giardina, G., Pontecorvi, V., Koes, D. R., McDermott, L. A., et al. (2015) · Oncotarget · doi:10.18632/oncotarget.6726 · Cited by 57 · see citing works
The KMT1A-GATA3-STAT3 Circuit Is a Novel Self-Renewal Signaling of Human Bladder Cancer Stem Cells
Yang, Z., He, L., Lin, K., Zhang, Y., Deng, A., Liang, Y., Li, C., & Wen, T. (2017) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-17-0882 · Cited by 57 · see citing works
Self-citationZhang, 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 · see citing works
Paiardini, A., Tramonti, A., Schirch, D., Guiducci, G., di Salvo, M. L., Fiascarelli, A., Giorgi, A., Maras, B., Cutruzzolà, F., & Contestabile, R. (2016) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2016.08.010 · Cited by 44 · see citing works
Tian, J., Mo, J., Xu, L., Zhang, R., Qiao, Y., Liu, B., Jiang, L., Ma, S., & Shi, G. (2020) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2020.109184 · Cited by 35 · see citing works
Du, L., Yang, F., Fang, H., Sun, H., Chen, Y., Xu, Y. K., Li, H. Z., Zheng, L., & Zhou, B. S. (2019) · The FASEB Journal · doi:10.1096/fj.201801559rr · Cited by 26 · see citing works
Cancer 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 · see citing works
Flagged first, then by citations
1 of the 56 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Membrez, M., Migliavacca, E., Christen, S., Yaku, K., Trieu, J., Lee, A. K., Morandini, F., Giner, M. P., Stiner, J., Makarov, M. V., et al. (2024) · Nature Metabolism · doi:10.1038/s42255-024-00997-x · Cited by 148 · see citing works
“…a potential link between trigonelline and a methyltransferase involved in one-carbon metabolism that will require further exploration, SHMT2 is unlikely to directly demethylate trigonelline because it is not a N -methyltransferase and is known to cross-talk with NAD + metabolism indirectly 37,38 .”
BackgroundSerine signaling governs metabolic homeostasis and health
He, L., Ding, Y., Zhou, X., Li, T., & Yin, Y. (2023) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2023.03.001 · Cited by 98 · see citing works
Zou, Z., Cheng, Q., Zhou, J., Guo, C., Hadjinicolaou, A. V., Salio, M., Liang, X., Yang, C., Du, Y., Yao, W., et al. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.113995 · Cited by 69 · see citing works
Liu, Z., Fan, M., Hou, J., Pan, S., Xu, Y., Zhang, H., Liu, C., Hao, X., Li, X., & Wang, H. (2023) · Cell Death and Disease · doi:10.1038/s41419-023-05677-4 · Cited by 36 · see citing works
Self-citationXing, Y., & Liu, C. (2025) · Cell Death Discovery · doi:10.1038/s41420-025-02683-7 · Cited by 32 · see citing works
The Beneficial Role of Sirtuin 1 in Preventive or Therapeutic Options of Neurodegenerative Diseases
Liu, H., Xu, S., Wang, C., Deng, Y. L., Xu, B., Yang, T., Sun, J., & Liu, W. (2022) · Neuroscience · doi:10.1016/j.neuroscience.2022.09.021 · Cited by 30 · see citing works
The role of serine metabolism in lung cancer: From oncogenesis to tumor treatment
Zhou, X., Tian, C., Cao, Y., Zhao, M., & Wang, K. (2023) · Frontiers in Genetics · doi:10.3389/fgene.2022.1084609 · Cited by 30 · see citing works
Kim, Y. H., Yoon, S. J., Kim, M., Kim, H. H., Song, Y. S., Jung, J. W., Han, D., Cho, S. W., Kwon, S. W., & Park, Y. J. (2023) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-23-2025 · Cited by 29 · see citing works
SHMT2 Promotes Gastric Cancer Development through Regulation of HIF1α/VEGF/STAT3 Signaling
Wang, W., Wang, M., Du, T., Hou, Z., You, S., Zhang, S., Ji, M., Xue, N., & Chen, X. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24087150 · Cited by 28 · see citing works
D-lactate and glycerol as potential biomarkers of sorafenib activity in hepatocellular carcinoma
Pedretti, S., Palermo, F., Braghin, M., Imperato, G., Tomaiuolo, P., Celikag, M., Boccazzi, M., Vallelonga, V., Dalt, L. D., Norata, G. D., et al. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02282-z · Cited by 18 · see citing works
Vitamin B6 deficiency cooperates with oncogenic Ras to induce malignant tumors in Drosophila
Pilesi, E., Tesoriere, G., Ferriero, A., Mascolo, E., Liguori, F., Argirò, L., Angioli, C., Tramonti, A., Contestabile, R., Volonté, C., et al. (2024) · Cell Death and Disease · doi:10.1038/s41419-024-06787-3 · Cited by 16 · see citing works
Sugarman, A. J., Huynh, L. D., Shabro, A., & Cristofano, A. D. (2023) · Cancer Letters · doi:10.1016/j.canlet.2023.216304 · Cited by 15 · see citing works
Deng, H., Wang, Y., Xiao, L., Feng, M., Dou, W., & Pan, Y. (2025) · npj Precision Oncology · doi:10.1038/s41698-025-00926-5 · Cited by 13 · see citing works
Han, W., Wang, S., Qi, Y., Wu, F., Tian, N., Qiang, B., & Peng, X. (2022) · iScience · doi:10.1016/j.isci.2022.104823 · Cited by 13 · see citing works
Limiting serine availability during tumor progression promotes muscle wasting in cancer cachexia
Pranzini, E., Muccillo, L., Nesi, I., Santi, A., Mancini, C., Lori, G., Genovese, M., Lottini, T., Comito, G., Caselli, A., et al. (2024) · Cell Death Discovery · doi:10.1038/s41420-024-02271-1 · Cited by 10 · see citing works
Su, S.-W., Chen, X., Wang, G., Li, P., Yang, T., Fang, K.-W., Wu, J., & Li, J. (2024) · Scientific Reports · doi:10.1038/s41598-024-58618-2 · Cited by 8 · see citing works
Wang, S.-Q., Liu, N., Zhang, Q., Li, B., Zhao, F.-Y., Li, C., Wang, H., & Liu, C. (2025) · Cell Death and Disease · doi:10.1038/s41419-025-07445-y · Cited by 8 · see citing works
MiR-383-5p inhibits the proliferation and migration of lung adenocarcinoma cells by targeting SHMT2
Bi, X., Wang, L., Li, H., Ma, Y., Guo, R., Yue, J., Kong, L., Gong, X., Jiao, F., Chinn, E., et al. (2024) · Journal of Cancer · doi:10.7150/jca.89733 · Cited by 7 · see citing works
Xu, X., Li, M., Xu, W., Wang, M., Wu, Y., Cheng, L., Li, J., Qin, Y., Liu, S., Yang, G., et al. (2024) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.4c00143 · Cited by 7 · see citing works
SHMT proteins: An emerging set of serine hydroxymethyltransferase in cancer
Fu, R., Sun, F., Wang, W., Wang, R., Zhang, H., He, X., Liu, A., & Yang, L. (2025) · Cellular Signalling · doi:10.1016/j.cellsig.2025.111977 · Cited by 7 · see citing works
Zhu, S., Liu, Y., Chen, H., Zhu, X., Liu, X., Xu, K., Sang, Y., Shang, L., Chong, W., & Li, L. (2025) · Clinical Medicine Insights Oncology · doi:10.1177/11795549251331755 · Cited by 6 · see citing works
Roles of non-coding RNAs in the metabolism and pathogenesis of bladder cancer
Sanya, D. R. A., & Onésime, D. (2023) · Human Cell · doi:10.1007/s13577-023-00915-5 · Cited by 6 · see citing works
Liu, D., Yi, H.-W., & Yi, C. (2025) · Antioxidants · doi:10.3390/antiox14121413 · Cited by 5 · see citing works
Zhou, Y., Kang, L., Xu, R., Zhao, D., Wang, J., Wu, J., Lin, H., Ding, Z., & Zou, Y. (2024) · Cellular Signalling · doi:10.1016/j.cellsig.2024.111219 · Cited by 5 · see citing works
Zirpoli, S., Copperman, N., Patel, S., Forrest, A., Hou, Z., Matherly, L. H., Loeb, D. M., & Cristofano, A. D. (2025) · Cancer Research Communications · doi:10.1158/2767-9764.crc-25-0218 · Cited by 4 · see citing works
Hu, X., Hu, T., Cao, S., Zheng, L., Ni, M., Shang, Q., Li, Y., Luo, H. Q., Zhao, N., Wang, L., et al. (2025) · Cancer Letters · doi:10.1016/j.canlet.2025.217963 · Cited by 4 · see citing works
Self-citationLyu, H., Hou, D., Liu, Y., Wang, J., & Sui, M. (2025) · The FASEB Journal · doi:10.1096/fj.202502544rr · Cited by 4 · see citing works
Yang, D., Peng, D., Zhou, Y., Qiang, Z., Wan, L., Xiang, F., Meng, Y., Xu, G., & Meng, Y. (2023) · Natural Product Research · doi:10.1080/14786419.2023.2295915 · Cited by 4 · see citing works
Chen, H., Wang, Z., Shi, J., & Peng, J. (2025) · Scientific Reports · doi:10.1038/s41598-025-86970-4 · Cited by 4 · see citing works
Wu, C., Fu, Q., Liu, J., Fu, J., Zhang, B., Zhou, J., Xu, J., Zhang, Y., Zhu, T., Yang, L., et al. (2026) · Journal of Orthopaedic Translation · doi:10.1016/j.jot.2026.101049 · Cited by 3 · see citing works
Self-citationZhao, Y., Chang, Z., Hu, B., Zhang, Q., Zhang, D., He, C., Guo, Y., Peng, Z., Chen, C., & Chen, Y. (2023) · Frontiers in Oncology · doi:10.3389/fonc.2023.1090542 · Cited by 3 · see citing works
Why is the tumor microenvironment disordered by NADH/NAD+ imbalance and how can we intervene?
Jing Jing, L. I., Zhang, T., Ma, T., Chen, T., Liu, X., & He, W. (2026) · Redox Biology · doi:10.1016/j.redox.2026.104145 · Cited by 3 · see citing works
Chen, L., Zhao, L., Ma, Z., Song, P., Zhou, X., Guo, M., Li, Z., Zhou, Y., Zhou, P., Xu, L., et al. (2025) · Chinese Medical Journal · doi:10.1097/cm9.0000000000003886 · Cited by 1 · see citing works
Reprogramming of nitrogen metabolism in tumors: mechanisms and therapeutic implications
Fang, J., Ling, J., Liu, X., Wang, Y., Huang, Y., Cao, Z., 邹燕梅, & Xiong, H. (2026) · Amino Acids · doi:10.1007/s00726-026-03517-1 · Cited by 1 · see citing works
Li, J.-Y., Zhang, X., & Sheng, R. (2026) · Journal of Translational Medicine · doi:10.1186/s12967-026-08044-x · Cited by 1 · see citing works
Bioengineered systems to exploit tumor microenvironment metabolism
Sanganoo, C., Caturegli, I., Mattes, Z. F., Ryan, J., Wong, W. W., & Grinstaff, M. W. (2026) · Trends in cancer · doi:10.1016/j.trecan.2026.04.003 · Cited by 1 · see citing works
de Oliveira, G. P., Zimmerman, A. J., Palu, C. C., Tran, V., Bogut, G., Chidester, S., Tigges, J., Vega, R. A., Aikawa, E. R., Jones, J. C., et al. (2026) · Molecular & Cellular Proteomics · doi:10.1016/j.mcpro.2026.101610 · Cited by 1 · see citing works
Interaction Analysis of SHMT1/2 Gene Variants with HCC in Chinese PatientsPreprint
Sun, Y., Gao, J., Shi, C., Liu, X., Zhang, F., Shi, X., Wang, Y., He, Y., Guo, W.-Z., & Zhang, S. (2022) · Research Square · doi:10.21203/rs.3.rs-2197291/v1
Chen, H., Wang, Z., Shi, J., & Peng, J. (2024) · Research Square · doi:10.21203/rs.3.rs-4176718/v1
Zirpoli, S., Copperman, N., Patel, S. D., Forrest, A., Hou, Z., Matherly, L. H., Loeb, D. M., & Cristofano, A. D. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.04.13.647987
Badr, E. A. E., Mekhail, Y. N., Hassan, K. S. A., & Assar, M. F. (2025) · Journal of Immunoassay and Immunochemistry · doi:10.1080/15321819.2025.2533800
Guo, X., & Li, G. (2025) · Frontiers in Genetics · doi:10.3389/fgene.2025.1694089
Serine Hydroxymethyltransferase in Cancer Cells
Гаврилюк, Л. А. (2025) · Biochemistry (Moscow) Supplement Series B Biomedical Chemistry · doi:10.1134/s1990750824601371
SHMT2 inhibition triggers mitochondrial apoptosis to suppress lung adenocarcinoma progression
Chen, Y., Zhang, X. H., Pang, X., Yang, Y., Lu, D., Zhao, J., Zhu, J., Du, W., Gu, C., Li, J., et al. (2026) · Journal of Translational Medicine · doi:10.1186/s12967-026-07975-9
Self-citationBetulin–Amino Acid Molecular Hybrids: Synthesis, Structure and Pharmacological Potential
Grymel, M., Naprawca, P., Dolniak-Budny, D., Tomczyk, M. D., Pielok, M., Nowrot, B., Skutnik, K., Erfurt, K., & Lalik, A. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27104445
SYVN1-mediated degradation of SHMT2 drives tubular injury progression via metabolic reprogramming
Li, S.-S., Xi, C. H. E. N., ZHANG, Q., Tang, J., Yu, L., & Liu, Q. (2026) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2026.08.014
Shen, S., Lim, M. A., Zheng, S., Piao, S., Kim, D. H., Cui, S., Kim, Y. I., Chang, J. W., Jung, S.-N., & Koo, B. S. (2026) · Antioxidants · doi:10.3390/antiox15101300
- Authors
- Zhang, Y., Liu, Z., Wang, X., Jian, H., Xiao, H., & Wen, T.
- Affiliations
- Chinese Academy of Sciences (CN)
- Corresponding author
- Wen, Tingyi
- Venue
- Cancer Gene Therapy
- Published
- 2022-04-14
- Volume
- 29
- Issue
- 10
- Pages
- 1514-1527
- ISSN
- 0929-1903 (ISSN-L)
- 1476-5500
- OpenAlex
- W4223927692
- Cited by
- 47
- References
- 56
- Citations by year
- 2026: 10 · 2025: 16 · 2024: 9 · 2023: 9 · 2022: 3
- FWCI
- 3.90
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Cancer Gene Therapy (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Keywords
- SHMT2, serine hydroxymethyltransferase, bladder cancer, apoptosis, reactive oxygen species, mitochondrial apoptosis, one-carbon metabolism, redox homeostasis, cell proliferation, serine metabolism, formate, N-acetylcysteine, cytochrome c release, Bcl-2 family proteins, caspase-3, mitochondrial membrane potential
- MeSH terms
- Urinary Bladder Neoplasms, Carbon, Cell Survival, Cysteine, Formates, Glycine, Humans, NAD, NADP, Serine, Glycine Hydroxymethyltransferase, Signal Transduction, Apoptosis, Reactive Oxygen Species, Proto-Oncogene Proteins c-bcl-2, Glutathione Disulfide, Cytochromes c, Cell Line, Tumor, Caspase 3
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