Skip to main content
SpringerLink
Log in

The MYC Network and Cancer

  • Chapter
  • First Online:
Book cover Signaling Pathways in Liver Diseases

Abstract

Deregulation of c-Myc (referred to as MYC] contributes to the development of the most human tumors [1–3]. In addition to MYC, the Myc gene family contains three related genes, N-Myc, L-Myc, and S-Myc, which are also implicated in the genesis of specific human tumors (for review, see ref [4]). MYC is a nuclear transcription factor, which is first identified as the cellular homologue of the cancer-causing gene in the avian myelocytomatosis retrovirus [5]. MYC functions in a heterodimeric complex with MAX to bind E-Box motifs in DNA, and transcriptionally regulates hundreds to thousands of target genes. The most recent estimates suggest that MYC could regulate as many as 15% of genes in genomes from flies to human [6]. A compilation of MYC-regulated genes and studies on MYC alterations in human cancers is available online at www.myccancergene.org [6]. This database emphasizes both the critical role of MYC in human cancers and the significance of MYC target genes in driving its oncogenic activity. The target genes are involved in diverse programs including cell cycle, cell growth, protein synthesis, cell adhesion and cytoskeleton, metabolism, apoptosis, angiogenesis, DNA repair, and microRNA [6–8]. The diversity of MYC target genes is illustrated in Fig. 24.1. Numerous excellent and comprehensive reviews have been written about MYC [9–12]. Therefore, in this chapter, we will focus mainly on the role of MYC in cancer with the emphasis on the most recent findings.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 139.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 249.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Nesbit CE, Tersak JM, Prochownik EV (1999) MYC oncogenes and human neoplastic disease. Oncogene 18: 3004–3016

    Article  CAS  PubMed  Google Scholar 

  2. Dang CV (1999) c-Myc target genes involved in cell growth, apoptosis, and metabolism. Mol Cell Biol 19:1–11

    CAS  PubMed  Google Scholar 

  3. Pelengaris S, Khan M, Evan G (2002) c-MYC: more than just a matter of life and death. Nat Rev Cancer 2:764–776

    Article  CAS  PubMed  Google Scholar 

  4. Adhikary S, Eilers M (2005) Transcriptional regulation and transformation by Myc proteins. Nat Rev Mol Cell Biol 6: 635–645

    Article  CAS  PubMed  Google Scholar 

  5. Bishop JM (1982) Retroviruses and cancer genes. In: George Kline SW (ed) Advances in cancer research, 37. Academic Press Inc., New York, pp 1–32

    Google Scholar 

  6. Dang CV, O’Donnell KA, Zeller KI et al (2006) The c-Myc target gene network. Semin Cancer Biol 16:253–264

    Article  CAS  PubMed  Google Scholar 

  7. Oster SK, Ho CS, Soucie EL et al (2002) The MYC oncogene: marvelously complex. Adv Cancer Res 84:81–154

    Article  CAS  PubMed  Google Scholar 

  8. Alitalo K, Schwab M (1986) Oncogene amplification in tumor cells. Adv Cancer Res 47:235–281

    Article  CAS  PubMed  Google Scholar 

  9. Meyer N, Penn LZ (2008) Reflecting on 25 years with MYC. Nat Rev Cancer 8:976–990

    Article  CAS  PubMed  Google Scholar 

  10. Eilers M, Eisenman RN (2008) Myc’s broad reach. Genes Dev 22:2755–2766

    Article  CAS  PubMed  Google Scholar 

  11. Secombe J, Pierce SB, Eisenman RN (2004) Myc: a weapon of mass destruction. Cell 117:153–156

    Article  CAS  PubMed  Google Scholar 

  12. Eisenman RN (2001) Deconstructing myc. Genes Dev 15: 2023–2030

    Article  CAS  PubMed  Google Scholar 

  13. Lau LF, Nathans D (1987) Expression of a set of growth-related immediate early genes in BALB/c 3 T3 cells: coordinate regulation with c-fos or c-myc. Proc Natl Acad Sci U S A 84:1182–1186

    Article  CAS  PubMed  Google Scholar 

  14. Lanahan A, Williams JB, Sanders LK et al (1992) Growth factor induced delayed early response genes. Mol Cell Biol 12:3919–3929

    CAS  PubMed  Google Scholar 

  15. Kim SY, Herbst A, Tworkowski KA et al (2003) Skp2 regulates Myc protein stability and activity. Mol Cell 11: 1177–1188

    Article  CAS  PubMed  Google Scholar 

  16. Salghetti SE, Kim SY, Tansey WP (1999) Destruction of Myc by ubiquitinmediated proteolysis: cancer-associated and transforming mutations stabilize Myc. EMBO J 18: 717–726

    Article  CAS  PubMed  Google Scholar 

  17. Lutterbach B, Hann SR (1999) c-Myc transactivation domain-associated kinases: questionable role for map kinases in c-Myc phosphorylation. J Cell Biochem 72: 483–491

    Article  CAS  PubMed  Google Scholar 

  18. Lutterbach B, Hann SR (1994) Hierarchical phosphorylation at N-terminal transformation-sensitive sites in c-Myc protein is regulated by mitogens and in mitosis. Mol Cell Biol 14:5510–5522

    CAS  PubMed  Google Scholar 

  19. Sears R, Leone G, DeGregori J et al (1999) Ras enhances Myc protein stability. Mol Cell 3:169–179

    Article  CAS  PubMed  Google Scholar 

  20. Yeh E, Cunningham M, Arnold H et al (2004) A signalling pathway controlling c-Myc degradation that impacts oncogenic transformation of human cells. Nat Cell Biol 6:308–318

    Article  CAS  PubMed  Google Scholar 

  21. Sakamuro D, Prendergast GC (1999) New Myc-interacting proteins: a second Myc network emerges. Oncogene 18: 2942–2954

    Article  CAS  PubMed  Google Scholar 

  22. Sakamuro D, Elliott KJ, Wechsler-Reya R et al (1996) BIN1 is a Novel MYC-interacting protein with features of a tumour suppressor. Nat Genet 14:69–77

    Article  CAS  PubMed  Google Scholar 

  23. Eilers M, Picard D, Yamamoto KR et al (1989) Chimaeras of myc oncoprotein and steroid receptors cause hormone-dependent transformation of cells. Nature 340:66–68

    Article  CAS  PubMed  Google Scholar 

  24. Eberhardy SR, Farnham PJ (2001) c-Myc mediates activation of the cad promoter via a post-RNApolymerase II recruitment mechanism. J Biol Chem 276:48562–48571

    CAS  PubMed  Google Scholar 

  25. Zeller KI, Haggerty TJ, Barrett JF et al (2001) Charac­terization of nucleophosmin (B23) as a Myc target by scanning chromatin immunoprecipitation. J Biol Chem 76: 48285–48291

    Google Scholar 

  26. Mao DY, Watson JD, Yan PS et al (2003) Analysis of Myc bound loci identified by CpG island arrays shows that Max is essential for Myc-dependent repression. Curr Biol 13:882–886

    Article  CAS  PubMed  Google Scholar 

  27. Haggerty TJ, Zeller KI, Osthus RC et al (2003) A strategy for identifying transcription factor binding sites reveals two classes of genomic c-Myc target sites. Proc Natl Acad Sci U S A 100:5313–5318

    Article  CAS  PubMed  Google Scholar 

  28. Coller HA, Grandori C, Tamayo P et al (2000) Expression analysis with oligonucleotide microarrays reveals that MYC regulates genes involved in growth, cell cycle, signaling, and adhesion. Proc Natl Acad Sci U S A 97:3260–3265

    Article  CAS  PubMed  Google Scholar 

  29. Guo QM, Malek RL, Kim S et al (2000) Identification of c-myc responsive genes using rat cDNA microarray. Cancer Res 60:5922–5928

    CAS  PubMed  Google Scholar 

  30. Schuldiner O, Benvenisty N (2001) A DNA microarray screen for genes involved in c-MYC and N-MYC oncogenesis in human tumors. Oncogene 20:4984–4994

    Article  CAS  PubMed  Google Scholar 

  31. Marinkovic D, Marinkovic T, Kokai E et al (2004) Identification of novel Myc target genes with a potential role in lymphomagenesis. Nucleic Acids Res 32:5368–5378

    Article  CAS  PubMed  Google Scholar 

  32. Lawlor ER, Soucek L, Brown-Swigart L et al (2006) Reversible kinetic analysis of Myc targets in vivo provides novel insights into Myc-mediated tumorigenesis. Cancer Res 66:4591–4601

    Article  CAS  PubMed  Google Scholar 

  33. O’Connell BC, Cheung AF, Simkevich CP et al (2003) A large scale genetic analysis of c-Myc-regulated gene expression patterns. J Biol Chem 278:12563–12573

    Article  PubMed  Google Scholar 

  34. Ellwood-Yen K, Graeber TG, Wongvipat J et al (2003) Myc-driven murine prostate cancer shares molecular features with human prostate tumors. Cancer Cell 4:223–238

    Article  CAS  PubMed  Google Scholar 

  35. Lee JS, Chu IS, Mikaelyan A et al (2004) Application of comparative functional genomics to identify best-fit mouse models to study human cancer. Nat Genet 36:1306–1311

    Article  CAS  PubMed  Google Scholar 

  36. Wu CH, Sahoo D, Arvanitis C et al (2008) Combined analysis of murine and human microarrays and ChIP analysis reveals genes associated with the ability of MYC to maintain tumorigenesis. PLoS Genet 4:1–16

    Article  Google Scholar 

  37. Sahoo D, Dill DL, Tibshirani R et al (2007) Extracting binary signals from microarray time-course data. Nucleic Acids Res 35:3705–3712

    Article  CAS  PubMed  Google Scholar 

  38. Liu J, Levens D (2006) Making myc. Curr Top Microbiol Immunol 302:1–32

    Article  CAS  PubMed  Google Scholar 

  39. Rabbitts PH, Watson JV, Lamond A et al (1985) Metabolism of c-myc gene products: c-myc mRNA and protein expression in the cell cycle. EMBO J 4:2009–2015

    CAS  PubMed  Google Scholar 

  40. Ramsay G, Evan GI, Bishop JM (1984) The protein encoded by the human proto-oncogene c-myc. Proc Natl Acad Sci U S A 81:7742–7746

    Article  CAS  PubMed  Google Scholar 

  41. Popescu NC, Zimonjic DB (2002) Chromosome-mediated alterations of the MYC gene in human cancer. J Cell Mol Med 6:151–159

    Article  CAS  PubMed  Google Scholar 

  42. Spencer CA, Groudine M (1991) Control of c-myc regulation in normal and neoplastic cells. Adv. Cancer Res 56:1–48

    Article  CAS  PubMed  Google Scholar 

  43. Sears R, Leone G, DeGregori J et al (1999) Ras enhances Myc protein stability. Mol Cell 3:169–79

    Article  CAS  PubMed  Google Scholar 

  44. He TC, Sparks AB, Rago C et al (1998) Identification of c-MYC as a target of the APC pathway. Science 281:1509–12

    Article  CAS  PubMed  Google Scholar 

  45. Kolligs FT, Bommer G, Goke B (2002) Wnt/beta-catenin/tcf signaling: a critical pathway in gastrointestinal tumorigenesis. Digestion 66:131–144

    Article  CAS  PubMed  Google Scholar 

  46. Evan G, Littlewood T (1998) A matter of life and cell death. Science 281:1317–1322

    Article  CAS  PubMed  Google Scholar 

  47. Lowe SW, Cepero E, Evan G (2004) Intrinsic tumour suppression. Nature 432:307–315

    Article  CAS  PubMed  Google Scholar 

  48. Eischen CM, Weber JD, Roussel MF et al (1999) Disruption of the ARF-Mdm2–p53 tumor suppressor pathway in Mycinduced lymphomagenesis. Genes Dev 13:2658–2669

    Article  CAS  PubMed  Google Scholar 

  49. Kamijo T, Weber JD, Zambetti G et al (1998) Functional and physical interactions of the ARF tumor suppressor with p53 and Mdm2. Proc Natl Acad Sci U S A 95:8292–8297

    Article  CAS  PubMed  Google Scholar 

  50. Schmitt CA, McCurrach ME, de Stanchina E et al (1999) INK4a/ARF mutations accelerate lymphomagenesis and promote chemoresistance by disabling p53. Genes Dev 13: 2670–2677

    Article  CAS  PubMed  Google Scholar 

  51. Zindy F, Eischen CM, Randle DH et al (1998) Myc signaling via the ARF tumor suppressor regulates p53-dependent apoptosis and immortalization. Genes Dev 12:2424–2433

    Article  CAS  PubMed  Google Scholar 

  52. Askew DS, Ashmun RA, Simmons BC et al (1991) Constitutive c-myc expression in an IL-3-dependent myeloid cell line suppresses cell cycle arrest and accelerates apoptosis. Oncogene 6:1915–1922

    CAS  PubMed  Google Scholar 

  53. Evan GI, Wyllie AH, Gilbert CS et al (1992) Induction of apoptosis in fibroblasts by c-myc protein. Cell 69: 119–128

    Article  CAS  PubMed  Google Scholar 

  54. Murphy DJ, Junttila MR, Pouyet L et al (2008) Distinct thresholds govern Myc’s biological output in vivo. Cancer Cell 14:447–457

    Article  CAS  PubMed  Google Scholar 

  55. Freie BW, Eisenman RN (2008) Ratcheting Myc. Cancer Cell 14:425–426

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratory of Experimental Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 37 Convent Drive, Bethesda, MD, 20892, USA

    Snorri S. Thorgeirsson & Valentina M. Factor

Authors
  1. Snorri S. Thorgeirsson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Valentina M. Factor
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Snorri S. Thorgeirsson .

Editor information

Editors and Affiliations

  1. Inselspital, Universität Bern, Murtenstr. 35, Bern, 3010, Switzerland

    Jean-Francois Dufour

  2. Klinik für Viszeral- und, Universitätsspital Zürich, Rämistr. 100, Zürich, 8091, Switzerland

    Pierre-Alain Clavien

Selected Readings

Selected Readings

1. Eisenman RN. Deconstructing myc. Genes Dev. 2001;15:2023-30 (comprehensive analysis of the problem derives from the apparent gap between Myc’s biological role and what is surmised to be its molecular function)

2. Eilers M, Eisenman RN. Myc’s broad reach. Genes Dev. 2008; 22:2755 (two major aspects of MYC - the nature of the genes and pathways that are targeted by Myc, and the role of MYC in stem cell and cancer biology - are reviewed in this article

3. Meyer N, Penn LZ. Reflecting on 25 years with MYC. Nat Rev Cancer. 2008; 8:976-990 (in this article the authors chronicle the major advances in our understanding of MYC biology since the discovery of MYC 25 years ago, and examine the future trends of MYC research)

Rights and permissions

Reprints and permissions

Copyright information

© 2010 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Thorgeirsson, S.S., Factor, V.M. (2010). The MYC Network and Cancer. In: Dufour, JF., Clavien, PA. (eds) Signaling Pathways in Liver Diseases. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-00150-5_24

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-00150-5_24

  • Published:

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-00149-9

  • Online ISBN: 978-3-642-00150-5

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation