Signaling in Control of Cell Growth and Metabolism

Overview

Journal Cold Spring Harb Perspect Biol

Specialties Biology
Molecular Biology

Date 2012 Jun 13

PMID 22687276

Citations 136

Authors

Patrick S Ward

Craig B Thompson

Affiliations

Soon will be listed here.

Abstract

Mammalian cells require growth-factor-receptor-initiated signaling to proliferate. Signal transduction not only initiates entry into the cell cycle, but also reprograms cellular metabolism. This instructional metabolic reprogramming is critical if the cell is to fulfill the anabolic and energetic requirements that accompany cell growth and division. Growth factor signaling mediated by the PI3K/Akt pathway plays a major role in regulating the cellular uptake of glucose, as well as the incorporation of this glucose carbon into lipids for membrane synthesis. Tyrosine-kinase-based regulation of key glycolytic enzymes such as pyruvate kinase also plays a critical role directing glucose carbon into anabolic pathways. In addition, the Myc transcription factor and mTOR kinase regulate the uptake and utilization of amino acids for protein and nucleic acid synthesis, as well as for the supply of intermediates to the mitochondrial Krebs cycle. However, the relationship between cellular signaling and metabolism is not unidirectional. Cells, by sensing levels of intracellular metabolites and the status of key metabolic pathways, can exert feedback control on signal transduction networks through multiple types of metabolite-derived protein modifications. These mechanisms allow cells to coordinate growth and division with their metabolic activity.

Citing Articles

Cultivation methods and biology of Lentinula edodes.

Song X, Shang X, Zhang M, Yu H, Zhang D, Tan Q Appl Microbiol Biotechnol. 2025; 109(1):63.

PMID: 40067479 PMC: 11897120. DOI: 10.1007/s00253-024-13387-w.

Mammalian mitochondrial inorganic polyphosphate (polyP) and cell signaling: Crosstalk between polyP and the activity of AMPK.

Da Costa R, Nichenko A, Perez M, Tokarska-Schlattner M, Kavehmoghaddam S, Hambardikar V Mol Metab. 2024; 91:102077.

PMID: 39617267 PMC: 11696858. DOI: 10.1016/j.molmet.2024.102077.

Cytochrome and cancer cell metabolism: A new perspective.

Alshehri B Saudi Pharm J. 2024; 32(12):102194.

PMID: 39564377 PMC: 11570848. DOI: 10.1016/j.jsps.2024.102194.

Machine learning approach in canine mammary tumour classification using rapid evaporative ionization mass spectrometry.

Abbate J, Mangraviti D, Brunetti B, Cafarella C, Rigano F, Iaria C Anal Bioanal Chem. 2024; 417(2):373-388.

PMID: 39562368 DOI: 10.1007/s00216-024-05656-4.

Stimulation of neutral lipid synthesis via viral growth factor signaling and ATP citrate lyase during vaccinia virus infection.

Pant A, Belhaouari D, Dsouza L, Yang Z J Virol. 2024; 98(11):e0110324.

PMID: 39475274 PMC: 11578090. DOI: 10.1128/jvi.01103-24.

References

Sengupta S, Peterson T, Sabatini D . Regulation of the mTOR complex 1 pathway by nutrients, growth factors, and stress. Mol Cell. 2010; 40(2):310-22. PMC: 2993060. DOI: 10.1016/j.molcel.2010.09.026. View

Chowdhury R, Yeoh K, Tian Y, Hillringhaus L, Bagg E, Rose N . The oncometabolite 2-hydroxyglutarate inhibits histone lysine demethylases. EMBO Rep. 2011; 12(5):463-9. PMC: 3090014. DOI: 10.1038/embor.2011.43. View

Cai L, Sutter B, Li B, Tu B . Acetyl-CoA induces cell growth and proliferation by promoting the acetylation of histones at growth genes. Mol Cell. 2011; 42(4):426-37. PMC: 3109073. DOI: 10.1016/j.molcel.2011.05.004. View

Isaacs J, Jung Y, Mole D, Lee S, Torres-Cabala C, Chung Y . HIF overexpression correlates with biallelic loss of fumarate hydratase in renal cancer: novel role of fumarate in regulation of HIF stability. Cancer Cell. 2005; 8(2):143-53. DOI: 10.1016/j.ccr.2005.06.017. View

Taha C, Liu Z, Jin J, Al-Hasani H, Sonenberg N, Klip A . Opposite translational control of GLUT1 and GLUT4 glucose transporter mRNAs in response to insulin. Role of mammalian target of rapamycin, protein kinase b, and phosphatidylinositol 3-kinase in GLUT1 mRNA translation. J Biol Chem. 1999; 274(46):33085-91. DOI: 10.1074/jbc.274.46.33085. View

Li B, Carey M, Workman J . The role of chromatin during transcription. Cell. 2007; 128(4):707-19. DOI: 10.1016/j.cell.2007.01.015. View

Porstmann T, Griffiths B, Chung Y, Delpuech O, Griffiths J, Downward J . PKB/Akt induces transcription of enzymes involved in cholesterol and fatty acid biosynthesis via activation of SREBP. Oncogene. 2005; 24(43):6465-81. DOI: 10.1038/sj.onc.1208802. View

Zhong H, Chiles K, Feldser D, Laughner E, Hanrahan C, Georgescu M . Modulation of hypoxia-inducible factor 1alpha expression by the epidermal growth factor/phosphatidylinositol 3-kinase/PTEN/AKT/FRAP pathway in human prostate cancer cells: implications for tumor angiogenesis and therapeutics. Cancer Res. 2000; 60(6):1541-5. View

Shatrov V, Sumbayev V, Zhou J, Brune B . Oxidized low-density lipoprotein (oxLDL) triggers hypoxia-inducible factor-1alpha (HIF-1alpha) accumulation via redox-dependent mechanisms. Blood. 2003; 101(12):4847-9. DOI: 10.1182/blood-2002-09-2711. View

10.

Hitosugi T, Kang S, Vander Heiden M, Chung T, Elf S, Lythgoe K . Tyrosine phosphorylation inhibits PKM2 to promote the Warburg effect and tumor growth. Sci Signal. 2009; 2(97):ra73. PMC: 2812789. DOI: 10.1126/scisignal.2000431. View

11.

Selak M, Armour S, MacKenzie E, Boulahbel H, Watson D, Mansfield K . Succinate links TCA cycle dysfunction to oncogenesis by inhibiting HIF-alpha prolyl hydroxylase. Cancer Cell. 2005; 7(1):77-85. DOI: 10.1016/j.ccr.2004.11.022. View

12.

Clower C, Chatterjee D, Wang Z, Cantley L, Vander Heiden M, Krainer A . The alternative splicing repressors hnRNP A1/A2 and PTB influence pyruvate kinase isoform expression and cell metabolism. Proc Natl Acad Sci U S A. 2010; 107(5):1894-9. PMC: 2838216. DOI: 10.1073/pnas.0914845107. View

13.

Osthus R, Shim H, Kim S, Li Q, Reddy R, Mukherjee M . Deregulation of glucose transporter 1 and glycolytic gene expression by c-Myc. J Biol Chem. 2000; 275(29):21797-800. DOI: 10.1074/jbc.C000023200. View

14.

Fang M, Shen Z, Huang S, Zhao L, Chen S, Mak T . The ER UDPase ENTPD5 promotes protein N-glycosylation, the Warburg effect, and proliferation in the PTEN pathway. Cell. 2010; 143(5):711-24. DOI: 10.1016/j.cell.2010.10.010. View

15.

Christofk H, Vander Heiden M, Harris M, Ramanathan A, Gerszten R, Wei R . The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth. Nature. 2008; 452(7184):230-3. DOI: 10.1038/nature06734. View

16.

Bauer D, Harris M, Plas D, Lum J, Hammerman P, Rathmell J . Cytokine stimulation of aerobic glycolysis in hematopoietic cells exceeds proliferative demand. FASEB J. 2004; 18(11):1303-5. PMC: 4458073. DOI: 10.1096/fj.03-1001fje. View

17.

Tang H, Hornstein E, Stolovich M, Levy G, Livingstone M, Templeton D . Amino acid-induced translation of TOP mRNAs is fully dependent on phosphatidylinositol 3-kinase-mediated signaling, is partially inhibited by rapamycin, and is independent of S6K1 and rpS6 phosphorylation. Mol Cell Biol. 2001; 21(24):8671-83. PMC: 100027. DOI: 10.1128/MCB.21.24.8671-8683.2001. View

18.

Gwinn D, Shackelford D, Egan D, Mihaylova M, Mery A, Vasquez D . AMPK phosphorylation of raptor mediates a metabolic checkpoint. Mol Cell. 2008; 30(2):214-26. PMC: 2674027. DOI: 10.1016/j.molcel.2008.03.003. View

19.

Christofk H, Vander Heiden M, Wu N, Asara J, Cantley L . Pyruvate kinase M2 is a phosphotyrosine-binding protein. Nature. 2008; 452(7184):181-6. DOI: 10.1038/nature06667. View

20.

Haigis M, Sinclair D . Mammalian sirtuins: biological insights and disease relevance. Annu Rev Pathol. 2010; 5:253-95. PMC: 2866163. DOI: 10.1146/annurev.pathol.4.110807.092250. View