Direct role of nucleotide metabolism in C-MYC-dependent proliferation of melanoma cells
Open accessAbstract
To identify C-MYC targets rate-limiting for proliferation of malignant melanoma, we stably inhibited C-MYC in several human metastatic melanoma lines via lentivirus-based shRNAs approximately to the levels detected in normal melanocytes. C-MYC depletion did not significantly affect levels of E2F1 protein reported to regulate expression of many S-phase specific genes, but resulted in the repression of several genes encoding enzymes rate-limiting for dNTP metabolism. These included thymidylate synthase (TS), inosine monophosphate dehydrogenase 2 (IMPDH2) and phosphoribosyl pyrophosphate synthetase 2 (PRPS2). C-MYC depletion also resulted in reduction in the amounts of deoxyribonucleoside triphosphates (dNTPs) and inhibition of proliferation. shRNA-mediated suppression of TS, IMPDH2 or PRPS2 resulted in the decrease of dNTP pools and retardation of the cell cycle progression of melanoma cells in a manner similar to that of C-MYC-depletion in those cells. Reciprocally, concurrent overexpression of cDNAs for TS, IMPDH2 and PRPS2 delayed proliferative arrest caused by inhibition of C-MYC in melanoma cells. Overexpression of C-MYC in normal melanocytes enhanced expression of the above enzymes and increased individual dNTP pools. Analysis of in vivo C-MYC interactions with TS, IMPDH2 and PRPS2 genes confirmed that they are direct C-MYC targets. Moreover, all three proteins express at higher levels in cells from several metastatic melanoma lines compared to normal melanocytes. Our data establish a novel functional link between C-MYC and dNTP metabolism and identify its role in proliferation of tumor cells.
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Other c-myc targets involved in nucleotide biosynthesis are TS, IMPDH1, and IMPDH2.
“Other targets of c-myc that are involved in nucleotide biosynthesis are thymidylate synthase (TS) and inosine monophosphate dehydrogenase 1 (IMPDH1) and 2 (IMPDH2) (Liu et al., 2008; Mannava et al., 2008).”
From The emerging hallmarks of cancer metabolism (2016) · cites this paper as Mannava et al., 2008
c-myc-regulated targets include PRPS2 and CAD.
“Among the c-myc-regulated targets are phosphoribosyl pyrophosphate synthetase 2 (PRPS2), which catalyzes a first step of purine biosynthesis, as well as carbamoyl phosphate synthetase II (CAD), which initiates the pyrimidine ring-building cascade (Cunningham et al., 2014; Eberhardy and Farnham, 2001; Mannava et al., 2008).”
From The emerging hallmarks of cancer metabolism (2016) · cites this paper as Mannava et al., 2008
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“Also, when MYC was inhibited through lentivirus-based shRNAs in human metastatic melanoma cell lines, the genes encoding enzymes important for dNTP metabolism were repressed and the amount of dNTPs were reduced (Mannava et al. 2008).”
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Ramzy, L., Nasr, M., Metwally, A. A., & Awad, G. A. S. (2017) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2017.04.005 · Cited by 106 · see citing works
“c-Myc (myelocytomatosis) expression has a significant role in the proliferation of melanoma cells (Mannava et al., 2008).”
Gmeiner, W. H., & Okechukwu, C. C. (2023) · Cancer Drug Resistance · doi:10.20517/cdr.2022.136 · Cited by 108 · see citing works
Furtado, C. M., Marcondes, M. C., Sola‐Penna, M., de Souza, M. L. S., & Zancan, P. (2012) · PLoS ONE · doi:10.1371/journal.pone.0030462 · Cited by 106 · see citing works
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Regulation of Cancer Metabolism by Oncogenes and Tumor Suppressors
Iurlaro, R., León‐Annicchiarico, C. L., & Muñoz‐Pinedo, C. (2014) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/b978-0-12-416618-9.00003-0 · Cited by 107 · see citing works
Regulatory mechanisms of one-carbon metabolism enzymes
Petrova, B., Maynard, A. G., Wang, P., & Kanarek, N. (2023) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2023.105457 · Cited by 103 · see citing works
“Similarly, C-MYC regulates nucleotide metabolism in melanoma cells by directly interacting with the promoters of nucleotide metabolism enzymes, including TYMS, IMP dehydrogenase 2, and phosphoribosyl pyrophosphate synthetase 2 (47).”
BackgroundAlterations in cancer cell metabolism: The Warburg effect and metabolic adaptation
Asgari, Y., Zabihinpour, Z., Salehzadeh‐Yazdi, A., Schreiber, F., & Masoudi‐Nejad, A. (2015) · Genomics · doi:10.1016/j.ygeno.2015.03.001 · Cited by 98 · see citing works
Long non-coding RNAs involved in cancer metabolic reprogramming
Liu, H., Luo, J., Luan, S., He, C., & Li, Z. (2018) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-018-2946-1 · Cited by 98 · see citing works
Glutamine Metabolism in Brain Tumors
Natarajan, S. K., & Venneti, S. (2019) · Cancers · doi:10.3390/cancers11111628 · Cited by 96 · see citing works
“While in elanomas, it is shown to enhance glutamine-derived nucleotide biosynthesis by upregulating expression of rate-limiting enzymes in deoxyribonucleotide (dNTP) metabolism [54].”
BackgroundDeoxyribonucleotides as genetic and metabolic regulators
Mathews, C. K. (2014) · The FASEB Journal · doi:10.1096/fj.14-251249 · Cited by 95 · see citing works
“Our laboratory has been involved in a collaboration with that of Mikhail Nikiforov (67) on control exerted by the C-MYC oncogene on dNTP metabolism.”
BackgroundInterplay between Cellular Metabolism and the DNA Damage Response in Cancer
Moretton, A., & Loizou, J. I. (2020) · Cancers · doi:10.3390/cancers12082051 · Cited by 93 · see citing works
Qian, X., Li, X., Tan, L., Lee, J.-H., Xia, Y., Cai, Q., Zheng, Y., Wang, H., Lorenzi, P. L., & Lu, Z. (2017) · Cancer Discovery · doi:10.1158/2159-8290.cd-17-0712 · Cited by 90 · see citing works
“In addition, PRPS2 was shown to be crucial for cancer cell survival (18-20).”
BackgroundGarrett, M. C., Sperry, J., Braas, D., Yan, W., Le, T. M., Mottahedeh, J., Ludwig, K., Eskin, A., Qin, Y., Levy, R., et al. (2018) · Cancer & Metabolism · doi:10.1186/s40170-018-0177-4 · Cited by 83 · see citing works
“The availability of nucleotides for DNA synthesis can be a rate-limiting step in cellular proliferation [47].”
BackgroundThe Intersection of Purine and Mitochondrial Metabolism in Cancer
Vitto, H. D., Arachchige, D., Richardson, B. C., & French, J. B. (2021) · Cells · doi:10.3390/cells10102603 · Cited by 88 · see citing works
“With respect to de novo purine biosynthesis, c-Myc binds to the bi-directional promoters of PPAT and PAICS to increase pathway throughput and support cell proliferation [77].”
BackgroundTwo sides of the Myc-induced DNA damage response: from tumor suppression to tumor maintenance
Campaner, S., & Amati, B. B. (2012) · Cell Division · doi:10.1186/1747-1028-7-6 · Cited by 87 · see citing works
“Recently, it was demonstrated that c-Myc is an important regulator of nucleotide biosynthesis and that its expression elevates nucleotide levels and cell proliferation [51,58].”
BackgroundMYC and the Control of DNA ReplicationPreprint
Dominguez-Sola, D., & Gautier, J. (2014) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a014423 · Cited by 86 · see citing works
Oncogene-Driven Metabolic Alterations in Cancer
Min, H., & Lee, H. (2017) · Biomolecules & Therapeutics · doi:10.4062/biomolther.2017.211 · Cited by 87 · see citing works
“MYC is also involved in the metabolic reprogramming of fatty acids, glutamine, proline, and nucleic acids by direct transcriptional regulation or indirect regulation utilizing microRNAs (Mannava et al., 2008; Gao et al., 2009; Liu et al., 2012; Edmunds et al., 2014).”
BackgroundMannava, S., Moparthy, K., Wheeler, L. J., Natarajan, V., Zucker, S. N., Fink, E. E., Im, M. M., Flanagan, S. A., Burhans, W. C., Zeitouni, N. C., et al. (2012) · American Journal Of Pathology · doi:10.1016/j.ajpath.2012.09.011 · Cited by 83 · see citing works
“Nucleotide triphosphate quantification Nucleotide triphosphates were extracted and assayed as described previously (17, 18).”
MethodKeppeke, G. D., Andrade, L. E. C., Grieshaber, S. S., & Chan, E. K. L. (2015) · Cell & Bioscience · doi:10.1186/2045-3701-5-1 · Cited by 82 · see citing works
“The amount of IMPDH2 is also influenced by cellular nucleotide pools, which are related to cellular activities like mitosis and protein synthesis [31,32].”
BackgroundMYC Rules: Leading Glutamine Metabolism toward a Distinct Cancer Cell Phenotype
Tambay, V., Raymond, V., & Bilodeau, M. (2021) · Cancers · doi:10.3390/cancers13174484 · Cited by 82 · see citing works
“Further characterization of this pathway by Liu et al. has identified PPAT, PFAS, and CAD genes as molecular targets of c-Myc, each having E-boxes, namely PPAT and CAD in their respective promoters, as well as in the first introns of PFAS and CAD [89].”
BackgroundInfluentialIntegrative network analysis of TCGA data for ovarian cancer
Zhang, Q., Burdette, J. E., & Wang, J.-P. (2014) · BMC Systems Biology · doi:10.1186/s12918-014-0136-9 · Cited by 80 · see citing works
“The edge from MYC to IMPHD2 confirms that MYC depletion results in repression of IMPHD2 (a gene coding rate-limiting enzyme) [25].”
BackgroundTeng, R., Liu, Z., Tang, H., Zhang, W., Chen, Y., Xu, R., Chen, L., Song, J., Liu, X., & Deng, H. (2019) · Redox Biology · doi:10.1016/j.redox.2019.101218 · Cited by 81 · see citing works
MYCN-driven fatty acid uptake is a metabolic vulnerability in neuroblastoma
Tao, L., Mohammad, M. A., Milazzo, G., Moreno‐Smith, M., Patel, T. D., Zorman, B., Badachhape, A., Hernandez, B. E., Wolf, A. B., Zeng, Z., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-31331-2 · Cited by 75 · see citing works
Killing SCLC: insights into how to target a shapeshifting tumorPreprint
Sutherland, K. D., Ireland, A. S., & Oliver, T. G. (2022) · Genes & Development · doi:10.1101/gad.349359.122 · Cited by 78 · see citing works
“ASCL1-low cell lines and tumors have higher expression of IMPDH1 and IMPDH2, known MYC target genes that are key for guanine nucleotide biosynthesis (Mannava et al. 2008).”
BackgroundMetabolic reprogramming of metastatic breast cancer and melanoma bylet-7amicroRNA
Serguienko, A., Grad, I., Wennerström, A. B., Meza‐Zepeda, L. A., Thiede, B., Stratford, E. W., Myklebost, O., & Munthe, E. (2014) · Oncotarget · doi:10.18632/oncotarget.3235 · Cited by 76 · see citing works
“Both TYMS and IMPDH2 are up-regulated by the MYC oncoprotein [32, 33], which is a target of let-7 , suggesting an indirect regulatory mechanism.”
Guanosine triphosphate links MYC-dependent metabolic and ribosome programs in small-cell lung cancer
Huang, F., Huffman, K. E., Wang, Z., Wang, X., Li, K., Cai, F., Yang, C., Cai, L., Shih, T. S., Zacharias, L. G., et al. (2020) · Journal of Clinical Investigation · doi:10.1172/jci139929 · Cited by 72 · see citing works
“As expected from the known relationship between MYC and nucleotides (10, 11), genes related to purine metabolism were highly correlated with MYC in pan-cancer tumor and cell line databases, and Gene Set Enrichment Analysis (GSEA) identified REACTOME_ Purine Metabolism as highly correlated with MYC (Supplemental Figure…”
BackgroundDeregulated transcription factors in cancer cell metabolisms and reprogramming
Kant, R., Manne, R., Anas, M., Penugurti, V., Chen, T., Pan, B., Hsu, C.-C., & Lin, H. (2022) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2022.10.001 · Cited by 72 · see citing works
DNA replication stress: oncogenes in the spotlight
Primo, L. M. F., & Teixeira, L. K. (2019) · Genetics and Molecular Biology · doi:10.1590/1678-4685gmb-2019-0138 · Cited by 88 · see citing works
“As mentioned earlier, MYC transcription factors induce expression of numerous genes involved in cellular proliferation and DNA replication, including the nucleotide biosynthesis pathway (Liu et al., 2008; Mannava et al., 2008).”
BackgroundReprogramming of macrophages employing gene regulatory and metabolic network models
Hörhold, F., Eisel, D., Oswald, M., Kolte, A., Röll, D., Osen, W., Eichmüller, S. B., & König, R. (2020) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1007657 · Cited by 69 · see citing works
“In summary, we identified short lists of transcription factors, most prominently CTCF, E2F1, MYC, PPARγ and STAT6, predicted to enable the reprogramming of M2-like macrophages into M1-like macrophages when their expression was knocked down.”
BackgroundInfluentialThe Interplay between Myc and CTP Synthase in Drosophila
Aughey, G., Grice, S. J., & Liu, J. (2016) · PLoS Genetics · doi:10.1371/journal.pgen.1005867 · Cited by 69 · see citing works
“Conversely, some studies have reported no changes being detected following dMyc knockdown [28,38].”
BackgroundObesity and Cancer Metabolism: A Perspective on Interacting Tumor–Intrinsic and Extrinsic Factors
Doerstling, S. S., O’Flanagan, C. H., & Hursting, S. D. (2017) · Frontiers in Oncology · doi:10.3389/fonc.2017.00216 · Cited by 67 · see citing works
“Myc activates enzymes involved in nucleotide synthesis (42, 43), and the mammalian target of rapamycin (mTOR), a master regulator of cell growth downstream of PI3K/Akt, also activates the PPP (44).”
BackgroundControl of cell metabolism by the epidermal growth factor receptor
Orofiamma, L. A., Vural, D., & Antonescu, C. N. (2022) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2022.119359 · Cited by 69 · see citing works
A second Warburg‐like effect in cancer metabolism: The metabolic shift of glutamine‐derived nitrogen
Kodama, M., & Nakayama, K. I. (2020) · BioEssays · doi:10.1002/bies.202000169 · Cited by 65 · see citing works
Rai, P. (2010) · Mutation Research/Genetic Toxicology and Environmental Mutagenesis · doi:10.1016/j.mrgentox.2010.07.010 · Cited by 65 · see citing works
“Ras enhances c-Myc protein stability [127] and that c-Myc expression affects deoxyribonucleotide pool metabolism [126], this is a likely scenario.”
BackgroundControl of the Antitumor Immune Response by Cancer Metabolism
Domblides, C., Lartigue, L., & Faustin, B. (2019) · Cells · doi:10.3390/cells8020104 · Cited by 61 · see citing works
“C-Myc is the principal driver of glutamine metabolism [12], which increases the expression of glutamine transporters and their metabolic enzymes [13].”
Bianchi, A., Rana, M. S., Foley, C. E., Paul, L. M., Lipchick, B. C., Moparthy, S., Moparthy, K., Fink, E. E., Bagati, A., Hurley, E. L., et al. (2017) · Nature Methods · doi:10.1038/nmeth.4404 · Cited by 63 · see citing works
Wawrzyniak, J. A., Bianchi, A., Bshara, W., Mannava, S., Ackroyd, J. J., Bagati, A., Omilian, A. R., Im, M. M., Fedtsova, N. G., Miecznikowski, J. C., et al. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.09.015 · Cited by 61 · see citing works
“Lentiviral and retroviral infection protocols were described previously (Mannava et al., 2008).”
BackgroundMethodInfluentialOncometabolites as biomarkers in thyroid cancer: a systematic review
Khatami, F., Payab, M., Sarvari, M., Gilany, K., Larijani, B. A., Arjmand, B., & Tavangar, S. M. (2019) · Cancer Management and Research · doi:10.2147/cmar.s188661 · Cited by 58 · see citing works
“In addition, the synthesis of purines and pyrimidine is upregulated in cancer cells, and the catalyzing enzymes of this pathway including thymidylate synthase and inosine synthetase 2 are subjected to Myc-induced upregulation.(112,113) Glutamine is a nitrogen source for multiple steps of both purine and pyrimidine syn…”
BackgroundDynamic modules of the coactivator SAGA in eukaryotic transcription
Cheon, Y., Kim, H., Park, K., Kim, M., & Lee, D. (2020) · Experimental & Molecular Medicine · doi:10.1038/s12276-020-0463-4 · Cited by 55 · see citing works
Combined Inactivation of CTPS1 and ATR Is Synthetically Lethal to MYC-Overexpressing Cancer Cells
Sun, Z., Zhang, Z., Wang, Q.-Q., & Liu, J.-L. (2022) · Cancer Research · doi:10.1158/0008-5472.can-21-1707 · Cited by 54 · see citing works
Tworkoski, K., Platt, J. T., Bacchiocchi, A., Bosenberg, M., Boggon, T. J., & Stern, D. F. (2013) · Pigment Cell & Melanoma Research · doi:10.1111/pcmr.12110 · Cited by 56 · see citing works
“In support of this notion, AXL correlated positively with multiple genes associated with melanoma invasion, including CDH2 andWNT5A (Table S2) (Qi et al., 2005; Weeraratna et al., 2002).”
BackgroundInfluentialCapitalizing on Synthetic Lethality of MYC to Treat Cancer in the Digital Age
Thng, D. K. H., Toh, T. B., & Chow, E. K. (2021) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2020.11.014 · Cited by 52 · see citing works
CD98hc (SLC3A2) sustains amino acid and nucleotide availability for cell cycle progression
Cano-Crespo, S., Chillarón, J., Junza, A., Fernández‐Miranda, G., García, J., Polte, C., de la Ballina, L. R., Ignatova, Z., Yanes, Ó., Zorzano, A., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-50547-9 · Cited by 55 · see citing works
De novo nucleotide biosynthetic pathway and cancer
Chen, J., Yang, S., Li, Y., Xu, Z., Zhang, P., Song, Q., Yao, Y., & Pei, H. (2022) · Genes & Diseases · doi:10.1016/j.gendis.2022.04.018 · Cited by 55 · see citing works
“For example, MYC directly binds the promoter regions of TS, UMPS, IMPDH2 and PRPS2 genes, and regulates these gene expression.(32,33) Cunningham et al also reported another mechanism by which MYC regulates PRPS2.”
BackgroundNatural Compounds' Activity against Cancer Stem-Like or Fast-Cycling Melanoma Cells
Sztiller-Sikorska, M., Koprowska, K., Majchrzak, K., Hartman, M. L., & Czyż, M. (2014) · PLoS ONE · doi:10.1371/journal.pone.0090783 · Cited by 53 · see citing works
“several enzymes of nucleotide biosynthesis [35].”
GTP metabolic reprogramming by IMPDH2: unlocking cancer cells’ fuelling mechanism
Kofuji, S., & Sasaki, A. T. (2020) · The Journal of Biochemistry · doi:10.1093/jb/mvaa085 · Cited by 52 · see citing works
Snaps and mends: DNA breaks and chromosomal translocations
Javadekar, S. M., & Raghavan, S. C. (2015) · FEBS Journal · doi:10.1111/febs.13311 · Cited by 53 · see citing works
Glutamine metabolism in cancer therapy
Nguyen, T.-L., & Durán, R. V. (2018) · Cancer Drug Resistance · doi:10.20517/cdr.2018.08 · Cited by 52 · see citing works
“Indeed, c-myc induces the transcription of glutamine transporters, such as SLC1A5/ASCT2, and also promotes the expression of glutamine-catabolized enzymes such as glutaminase 1 (GLS1) and carbamoyl-phosphate synthetase 2 - aspartate transcarbamylase - dihydroorotase (CAD), in order to encourage glutamine uptake by con…”
BackgroundSequential adaptive changes in a c-Myc-driven model of hepatocellular carcinoma
Dolezal, J. M., Wang, H., Kulkarni, S., Jackson, L. E., Lu, J. L., Ranganathan, S., Goetzman, E. S., Bharathi, S. S., Beezhold, K., Byersdorfer, C. A., et al. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.m117.782052 · Cited by 49 · see citing works
“scripts was de-regulated as also described for Myc overexpression in vitro (39).”
BackgroundBianchi, A., Wawrzyniak, J. A., Bagati, A., Marvin, E. K., Ackroyd, J. J., Moparthy, S., Bshara, W., Fink, E. E., Foley, C. E., Morozevich, G. E., et al. (2015) · Cell Death and Differentiation · doi:10.1038/cdd.2015.47 · Cited by 50 · see citing works
“IMPDH1 and IMPDH2 are rate-limiting enzymes of de novo guanylate biosynthesis (Figure 1a) and their expression is elevated in tumor cells.(7,33,34) A specific inhibitor of IMPDH”
BackgroundMYC-induced metabolic stress and tumorigenesis
Wolpaw, A. J., & Dang, C. V. (2018) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2018.05.003 · Cited by 52 · see citing works
Topical and Targeted Delivery of siRNAs to Melanoma Cells Using a Fusion Peptide Carrier
Ruan, R., Chen, M., Sun, S., Wei, P., Zou, L., Liu, J., Gao, D. Y., Wen, L., & Ding, W. (2016) · Scientific Reports · doi:10.1038/srep29159 · Cited by 48 · see citing works
Targeting cancer-specific metabolic pathways for developing novel cancer therapeutics
Pal, S., Sharma, A. K., Mathew, S. P., & Jaganathan, B. G. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.955476 · Cited by 49 · see citing works
Adipose tissue dysfunction and its effects on tumor metabolism
Diedrich, J. D., Chkourko, H., & Podgorski, I. (2015) · Hormone Molecular Biology and Clinical Investigation · doi:10.1515/hmbci-2014-0045 · Cited by 46 · see citing works
“The c-MYC transcription factor is also known to regulate key proteins involved in both nucleic acid synthesis and fatty acid synthesis, processes utilized by tumor cells to meet the demands of rapid cellular division, which underlines its role as a crucial regulator of cellular metabolism [183, 184].”
BackgroundChong, Y. C., Toh, T. B., Chan, Z., Lin, Q. X. X., Thng, D. K. H., Hooi, L., Ding, Z., Shuen, T. W. H., Toh, H. C., Dan, Y. Y., et al. (2020) · Hepatology Communications · doi:10.1002/hep4.1559 · Cited by 45 · see citing works
Interplay Between Metabolism and Oncogenic Process: Role of microRNAs
Arora, A., Singh, S. P., Bhatt, A. N., Pandey, S., Sandhir, R., & Dwarakanath, B. S. R. (2015) · Translational Oncogenomics · doi:10.4137/tog.s29652 · Cited by 43 · see citing works
Metabolic Pathways, Enzymes, and Metabolites: Opportunities in Cancer Therapy
Kumar, R., Mishra, A., Gautam, P., Feroz, Z., Vijayaraghavalu, S., Likos, E., Shukla, G. C., & Kumar, M. (2022) · Cancers · doi:10.3390/cancers14215268 · Cited by 48 · see citing works
- Authors
- Mannava, S., Grachtchouk, V., Wheeler, L. J., Im, M., Zhuang, D., Slavina, E. G., Mathews, C. K., Shewach, D. S., & Nikiforov, M. A.
- Affiliations
- Roswell Park Comprehensive Cancer Center (US)
- Venue
- Cell Cycle
- Publisher
- Informa UK Limited
- Published
- 2008-08
- Volume
- 7
- Issue
- 15
- Pages
- 2392-2400
- ISSN
- 1538-4101 (ISSN-L)
- 1551-4005
- PMC
- PMC3744895
- OpenAlex
- W2087539641
- Cited by
- 257
- References
- 37
- Citations by year
- 2026: 10 · 2025: 12 · 2024: 29 · 2023: 15 · 2022: 26 · 2021: 20 · 2020: 19 · 2019: 21 · 2018: 11 · 2017: 18 · 2016: 13 · 2015: 17 · 2014: 14 · 2013: 6 · 2012: 6
- FWCI
- 2.75
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- Cell Cycle (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (R01CA076581, 5P30 CA 46592, R01CA083081, R01CA120244, R01-CA120244-A1, P30CA046592)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Molecular Research
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
- Keywords
- c-Myc, melanoma, nucleotide metabolism, dNTP pools, thymidylate synthase, IMPDH2, PRPS2, cell proliferation, cell cycle progression, shRNA knockdown, direct transcriptional targets, metastatic melanoma, melanocytes
- MeSH terms
- Humans, IMP Dehydrogenase, Melanocytes, Melanoma, Nucleotides, Promoter Regions, Genetic, Protein Binding, Ribose-Phosphate Pyrophosphokinase, Thymidylate Synthase, Transfection, Tumor Cells, Cultured, Gene Expression Regulation, Enzymologic, Gene Expression Regulation, Neoplastic, Proto-Oncogene Proteins c-myc, RNA, Small Interfering, Cell Proliferation
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