Regulation of cancer cell metabolism: Oncogenic MYC in the driver’s seat
Open accessAbstract
Cancer cells must rewire cellular metabolism to satisfy the demands of unbridled growth and proliferation. As such, most human cancers differ from normal counterpart tissues by a plethora of energetic and metabolic reprogramming. Transcription factors of the MYC family are deregulated in up to 70% of all human cancers through a variety of mechanisms. Oncogenic levels of MYC regulates almost every aspect of cellular metabolism, a recently revisited hallmark of cancer development. Meanwhile, unrestrained growth in response to oncogenic MYC expression creates dependency on MYC-driven metabolic pathways, which in principle provides novel targets for development of effective cancer therapeutics. In the current review, we summarize the significant progress made toward understanding how MYC deregulation fuels metabolic rewiring in malignant transformation.
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c-Myc is the master regulator of the metabolic network, affecting different metabolic processes and transactivating almost all genes that code for enzymes of glycolysis and one-carbon metabolism.
“c-Myc is known as the master regulator of the metabolic network, affecting different metabolic processes and transactivating almost all genes that code for enzymes of glycolysis and one-carbon metabolism [35,36,37].”
From 20-Hydroxyecdysone Boosts Energy Production and Biosynthetic Processes in Non-Transformed Mouse Cells (2024) · cites this paper as [35]
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Direct Phosphorylation and Stabilization of MYC by Aurora B Kinase Promote T-cell Leukemogenesis
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Regulation of OGT by URI in Response to Glucose Confers c-MYC-Dependent Survival Mechanisms
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Myc promotes glutaminolysis in human neuroblastoma through direct activation of glutaminase 2
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Coordination of glucose and glutamine utilization by an expanded Myc network
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The MYC oncogene — the grand orchestrator of cancer growth and immune evasion
Dhanasekaran, R., Deutzmann, A., Mahauad‐Fernandez, W. D., Hansen, A. S., Gouw, A. M., & Felsher, D. W. (2021) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-021-00549-2 · Cited by 1,010 · see citing works
Nucleotide metabolism: a pan-cancer metabolic dependency
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Amino acid metabolism in tumor biology and therapy
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Causal integration of multi‐omics data with prior knowledge to generate mechanistic hypotheses
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Cancer metabolism and tumor microenvironment: fostering each other?
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Lactate controls cancer stemness and plasticity through epigenetic regulation
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Disruption of the circadian clock drives Apc loss of heterozygosity to accelerate colorectal cancer
Chun, S. K., Fortin, B. M., Fellows, R. C., Habowski, A. N., Verlande, A., Song, W. A., Mahieu, A. L., Lefebvre, A. E. Y. T., Sterrenberg, J. N., Vélez, L. M., et al. (2022) · Science Advances · doi:10.1126/sciadv.abo2389 · Cited by 106 · see citing works
Reactive oxygen species produced by altered tumor metabolism impacts cancer stem cell maintenance
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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
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Deubiquitination of MYC by OTUB1 contributes to HK2 mediated glycolysis and breast tumorigenesis
Han, X., Ren, C., Lü, C., Qiao, P., Yang, T., & Yu, Z. (2022) · Cell Death and Differentiation · doi:10.1038/s41418-022-00971-8 · Cited by 101 · see citing works
Regulation and targeting of SREBP-1 in hepatocellular carcinoma
Su, F., & Koeberle, A. (2023) · Cancer and Metastasis Reviews · doi:10.1007/s10555-023-10156-5 · Cited by 100 · see citing works
The biogenesis and biological function of PIWI-interacting RNA in cancer
Chen, S., Ben, S., Xin, J., Li, S., Zheng, R., Wang, H., Fan, L., Du, M., Zhang, Z., & Wang, M. (2021) · Journal of Hematology & Oncology · doi:10.1186/s13045-021-01104-3 · Cited by 87 · see citing works
USP43 stabilizes c-Myc to promote glycolysis and metastasis in bladder cancer
Li, M., Yu, J., Ju, L., Wang, Y., Jin, W., Zhang, R., Wan, X., Ji, M., Du, W., Wang, G., et al. (2024) · Cell Death and Disease · doi:10.1038/s41419-024-06446-7 · Cited by 83 · see citing works
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MYC and KRAS cooperation: from historical challenges to therapeutic opportunities in cancer
Casacuberta‐Serra, S., González-Larreategui, Í., Capitán-Leo, D., & Soucek, L. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01907-z · Cited by 80 · see citing works
Current Status and Prospects of Targeted Therapy for Osteosarcoma
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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 74 · see citing works
The pyruvate dehydrogenase complex: Life’s essential, vulnerable and druggable energy homeostat
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Control 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
Vitamin B5 supports MYC oncogenic metabolism and tumor progression in breast cancer
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Linking Metabolic Reprogramming, Plasticity and Tumor Progression
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The crosstalk between metabolism and translation
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Targeting MYC-enhanced glycolysis for the treatment of small cell lung cancer
Cargill, K. R., Stewart, C. A., Park, E. M., Ramkumar, K., Gay, C. M., Cardnell, R. J., Wang, Q., Diao, L., Shen, L., Fan, Y.-H., et al. (2021) · Cancer & Metabolism · doi:10.1186/s40170-021-00270-9 · Cited by 62 · see citing works
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Identification and experimental validation of druggable epigenetic targets in hepatoblastoma
Clavería-Cabello, A., Herranz, J. M., Latasa, M. U., Arechederra, M., Uriarte, I., Pineda‐Lucena, A., Prósper, F., Berraondo, P., Alonso, C., Sangro, B., et al. (2023) · Journal of Hepatology · doi:10.1016/j.jhep.2023.05.031 · Cited by 55 · see citing works
Metabolic reprograming of MDSCs within tumor microenvironment and targeting for cancer immunotherapy
Li, Q., & Xiang, M. (2021) · Acta Pharmacologica Sinica · doi:10.1038/s41401-021-00776-4 · Cited by 54 · see citing works
Single-cell transcriptome analyses reveal microglia types associated with proliferative retinopathy
Liu, Z., Shi, H., Xu, J., Yang, Q., Ma, Q., Mao, X., Xu, Z., Zhou, Y., Da, Q., Cai, Y., et al. (2022) · JCI Insight · doi:10.1172/jci.insight.160940 · Cited by 53 · see citing works
Dong, T., Hu, G., Fan, Z., Wang, H., Gao, Y., Wang, S., Xu, H., Yaffe, M. B., Heiden, M. G. V., Lv, G., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-45167-5 · Cited by 63 · see citing works
Ahmad, H. I., Jabbar, A., Mushtaq, N., Javed, Z., Hayyat, M. U., Bashir, J., Naseeb, I., Abideen, Z. U., Ahmad, N., & Chen, J. (2022) · Frontiers in Veterinary Science · doi:10.3389/fvets.2022.827407 · Cited by 59 · see citing works
Targeting mitochondrial metabolism for metastatic cancer therapy
Passaniti, A., Kim, M. S., Polster, B. M., & Shapiro, P. S. (2022) · Molecular Carcinogenesis · doi:10.1002/mc.23436 · Cited by 53 · see citing works
FLI1 promotes IFN-γ-induced kynurenine production to impair anti-tumor immunity
Chen, E., Wu, J., Huang, J., Zhu, W., Sun, H., Wang, X., Lin, D., Li, X., Shi, D., Liu, Z.-Q., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-48397-9 · Cited by 52 · see citing works
RNA polymerase II at histone genes predicts outcome in human cancer
Henikoff, S., Zheng, Y., Paranal, R. M., Xu, Y., Greene, J. E., Henikoff, J. G., Russell, Z. R., Szulzewsky, F., Thirimanne, H. N., Kugel, S., et al. (2025) · Science · doi:10.1126/science.ads2169 · Cited by 50 · see citing works
The Crosstalk Between Signaling Pathways and Cancer Metabolism in Colorectal Cancer
Hon, K. W., Abidin, S. A. Z., Othman, I., & Naidu, R. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.768861 · Cited by 51 · see citing works
Metabolomics and the Multi-Omics View of Cancer
Wishart, D. S. (2022) · Metabolites · doi:10.3390/metabo12020154 · Cited by 51 · see citing works
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Non-coding RNAs: emerging biomarkers and therapeutic targets in cancer and inflammatory diseases
Abdelmonem, B. H., Kamal, L. T., Wardy, L. W., Ragheb, M., Hanna, M. M., Elsharkawy, M., & Abdelnaser, A. (2025) · Frontiers in Oncology · doi:10.3389/fonc.2025.1534862 · Cited by 52 · see citing works
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Restoration of the molecular clock is tumor suppressive in neuroblastoma
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MYC 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 45 · see citing works
Deregulated transcription factors in the emerging cancer hallmarks
Hasan, A., Khan, N. A., Shahab Uddin, M. S., Khan, A. Q., & Steinhoff, M. S. (2023) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2023.12.001 · Cited by 43 · see citing works
De novo pyrimidine synthesis fuels glycolysis and confers chemoresistance in gastric cancer
He, D., Chen, M., Chang, L., Gu, J., Liu, F., Gao, X., & Ruan, Y. (2022) · Cancer Letters · doi:10.1016/j.canlet.2022.215837 · Cited by 45 · see citing works
Tetracycline antibiotics: Potential anticancer drugs
Li, J., Qin, Y., Zhao, C., Zhang, Z., & Zhou, Z. (2023) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2023.175949 · Cited by 43 · see citing works
Yang, J., Chen, F., Lang, L., Yang, F., Fu, Z., Martínez, J., Cho, A., Saba, N. F., & Teng, Y. (2024) · Cancer Research · doi:10.1158/0008-5472.can-24-0254 · Cited by 43 · see citing works
MYC—an emerging player in mitochondrial diseases
Purhonen, J., Klefström, J. T., & Kallijärvi, J. (2023) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2023.1257651 · Cited by 40 · see citing works
Stem Cells in Cancer: From Mechanisms to Therapeutic Strategies
Haddadin, L., & Sun, X. S. (2025) · Cells · doi:10.3390/cells14070538 · Cited by 44 · see citing works
USP29 coordinates MYC and HIF1α stabilization to promote tumor metabolism and progression
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- Authors
- Dong, Y., Tu, R., Liu, H., & Qing, G.
- Affiliations
- Wuhan University (CN)
- Corresponding author
- Qing, Guoliang
- Venue
- Signal Transduction and Targeted Therapy
- Published
- 2020-07-10
- Volume
- 5
- Issue
- 1
- Pages
- 124-124
- ISSN
- 2059-3635 (ISSN-L)
- PMC
- PMC7351732
- OpenAlex
- W3041824636
- Cited by
- 405
- References
- 120
- Citations by year
- 2026: 84 · 2025: 87 · 2024: 71 · 2023: 48 · 2022: 58 · 2021: 51 · 2020: 6
- FWCI
- 4.15
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Signal Transduction and Targeted Therapy (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81830084, 81725013)
- Wuhan University (TFJC2018005)
- Fundamental Research Funds for the Central Universities (2042020kf0215)
- National Science Fund for Distinguished Young Scholars (81725013)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Keywords
- c-Myc, cancer metabolism, metabolic reprogramming, malignant transformation, cancer therapeutics, metabolic dependencies
- MeSH terms
- Animals, Cell Transformation, Neoplastic, Humans, Neoplasms, Gene Expression Regulation, Neoplastic, Proto-Oncogene Proteins c-myc
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