Metabolic Signatures of Cancer Cells and Stem Cells

Overview

Journal Nat Metab

Publisher Springer Nature

Specialty Endocrinology

Date 2019 Jun 28

PMID 31245788

Citations 144

Authors

Andrew M Intlekofer

Lydia W S Finley

Affiliations

Soon will be listed here.

Abstract

In contrast to terminally differentiated cells, cancer cells and stem cells retain the ability to re-enter the cell cycle and proliferate. In order to proliferate, cells must increase the uptake and catabolism of nutrients to support anabolic cell growth. Intermediates of central metabolic pathways have emerged as key players that can influence cell differentiation 'decisions', processes relevant for both oncogenesis and normal development. Consequently, how cells rewire metabolic pathways to support proliferation may have profound consequences for cellular identity. Here, we discuss the metabolic programs that support proliferation and explore how metabolic states are intimately entwined with the cell fate decisions that characterize stem cells and cancer cells. By comparing the metabolism of pluripotent stem cells and cancer cells, we hope to illuminate common metabolic strategies as well as distinct metabolic features that may represent specialized adaptations to unique cellular demands.

Citing Articles

Metaboloepigenetics: Role in the Regulation of Flow-Mediated Endothelial (Dys)Function and Atherosclerosis.

Santos F, Sum H, Yan D, Brewer A Cells. 2025; 14(5).

PMID: 40072106 PMC: 11898952. DOI: 10.3390/cells14050378.

Sirt6 loss activates Got1 and facilitates cleft palate through abnormal activating glycolysis.

Wang X, Zhao X, Zheng X, Peng X, Chen J, Wang Y Cell Death Dis. 2025; 16(1):159.

PMID: 40050262 PMC: 11885815. DOI: 10.1038/s41419-025-07465-8.

Chlorogenic acid promotes fatty acid beta-oxidation to increase hESCs proliferation and lipid synthesis.

Zong M, Ji J, Wang Q, Cai Y, Chen L, Zhang L Sci Rep. 2025; 15(1):7095.

PMID: 40016322 PMC: 11868603. DOI: 10.1038/s41598-025-91582-z.

Hsp90α promotes lipogenesis by stabilizing FASN and promoting FASN transcription via LXRα in hepatocellular carcinoma.

Deng Z, Liu L, Xie G, Zheng Z, Li J, Tan W J Lipid Res. 2024; 66(1):100721.

PMID: 39645039 PMC: 11745951. DOI: 10.1016/j.jlr.2024.100721.

IDH Mutations in Glioma: Molecular, Cellular, Diagnostic, and Clinical Implications.

Choate K, Pratt E, Jennings M, Winn R, Mann P Biology (Basel). 2024; 13(11).

PMID: 39596840 PMC: 11592129. DOI: 10.3390/biology13110885.

References

Beaudin A, Stover P . Insights into metabolic mechanisms underlying folate-responsive neural tube defects: a minireview. Birth Defects Res A Clin Mol Teratol. 2009; 85(4):274-84. PMC: 4435943. DOI: 10.1002/bdra.20553. View

Luengo A, Gui D, Vander Heiden M . Targeting Metabolism for Cancer Therapy. Cell Chem Biol. 2017; 24(9):1161-1180. PMC: 5744685. DOI: 10.1016/j.chembiol.2017.08.028. View

Kong H, Chandel N . Regulation of redox balance in cancer and T cells. J Biol Chem. 2017; 293(20):7499-7507. PMC: 5961053. DOI: 10.1074/jbc.TM117.000257. View

Chantranupong L, Wolfson R, Sabatini D . Nutrient-sensing mechanisms across evolution. Cell. 2015; 161(1):67-83. PMC: 4384161. DOI: 10.1016/j.cell.2015.02.041. View

Schvartzman J, Thompson C, Finley L . Metabolic regulation of chromatin modifications and gene expression. J Cell Biol. 2018; 217(7):2247-2259. PMC: 6028552. DOI: 10.1083/jcb.201803061. View

Weinberger L, Ayyash M, Novershtern N, Hanna J . Dynamic stem cell states: naive to primed pluripotency in rodents and humans. Nat Rev Mol Cell Biol. 2016; 17(3):155-69. DOI: 10.1038/nrm.2015.28. View

Martello G, Smith A . The nature of embryonic stem cells. Annu Rev Cell Dev Biol. 2014; 30:647-75. DOI: 10.1146/annurev-cellbio-100913-013116. View

Fan J, Kamphorst J, Mathew R, Chung M, White E, Shlomi T . Glutamine-driven oxidative phosphorylation is a major ATP source in transformed mammalian cells in both normoxia and hypoxia. Mol Syst Biol. 2013; 9:712. PMC: 3882799. DOI: 10.1038/msb.2013.65. View

Hosios A, Hecht V, Danai L, Johnson M, Rathmell J, Steinhauser M . Amino Acids Rather than Glucose Account for the Majority of Cell Mass in Proliferating Mammalian Cells. Dev Cell. 2016; 36(5):540-9. PMC: 4766004. DOI: 10.1016/j.devcel.2016.02.012. View

10.

Pavlova N, Thompson C . The Emerging Hallmarks of Cancer Metabolism. Cell Metab. 2016; 23(1):27-47. PMC: 4715268. DOI: 10.1016/j.cmet.2015.12.006. View

11.

DeBerardinis R, Chandel N . Fundamentals of cancer metabolism. Sci Adv. 2016; 2(5):e1600200. PMC: 4928883. DOI: 10.1126/sciadv.1600200. View

12.

Carey B, Finley L, Cross J, Allis C, Thompson C . Intracellular α-ketoglutarate maintains the pluripotency of embryonic stem cells. Nature. 2014; 518(7539):413-6. PMC: 4336218. DOI: 10.1038/nature13981. View

13.

Tohyama S, Fujita J, Hishiki T, Matsuura T, Hattori F, Ohno R . Glutamine Oxidation Is Indispensable for Survival of Human Pluripotent Stem Cells. Cell Metab. 2016; 23(4):663-74. DOI: 10.1016/j.cmet.2016.03.001. View

14.

Boroughs L, DeBerardinis R . Metabolic pathways promoting cancer cell survival and growth. Nat Cell Biol. 2015; 17(4):351-9. PMC: 4939711. DOI: 10.1038/ncb3124. View

15.

Chung S, Dzeja P, Faustino R, Perez-Terzic C, Behfar A, Terzic A . Mitochondrial oxidative metabolism is required for the cardiac differentiation of stem cells. Nat Clin Pract Cardiovasc Med. 2007; 4 Suppl 1:S60-7. PMC: 3232050. DOI: 10.1038/ncpcardio0766. View

16.

Zhou W, Choi M, Margineantu D, Margaretha L, Hesson J, Cavanaugh C . HIF1α induced switch from bivalent to exclusively glycolytic metabolism during ESC-to-EpiSC/hESC transition. EMBO J. 2012; 31(9):2103-16. PMC: 3343469. DOI: 10.1038/emboj.2012.71. View

17.

Zhang J, Khvorostov I, Hong J, Oktay Y, Vergnes L, Nuebel E . UCP2 regulates energy metabolism and differentiation potential of human pluripotent stem cells. EMBO J. 2011; 30(24):4860-73. PMC: 3243621. DOI: 10.1038/emboj.2011.401. View

18.

Gu W, Gaeta X, Sahakyan A, Chan A, Hong C, Kim R . Glycolytic Metabolism Plays a Functional Role in Regulating Human Pluripotent Stem Cell State. Cell Stem Cell. 2016; 19(4):476-490. PMC: 5055460. DOI: 10.1016/j.stem.2016.08.008. View

19.

Moussaieff A, Rouleau M, Kitsberg D, Cohen M, Levy G, Barasch D . Glycolysis-mediated changes in acetyl-CoA and histone acetylation control the early differentiation of embryonic stem cells. Cell Metab. 2015; 21(3):392-402. DOI: 10.1016/j.cmet.2015.02.002. View

20.

Cliff T, Wu T, Boward B, Yin A, Yin H, Glushka J . MYC Controls Human Pluripotent Stem Cell Fate Decisions through Regulation of Metabolic Flux. Cell Stem Cell. 2017; 21(4):502-516.e9. PMC: 5644510. DOI: 10.1016/j.stem.2017.08.018. View