Skip to main content
SpringerLink
Log in

An “-omycs” Toolbox to Work with MYC

  • Protocol
  • First Online:
The Myc Gene

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2318))

Abstract

The MYC transcription factor coordinates a wide range of intra- and extracellular processes associated with tissue proliferation and regeneration. While these processes are typically tightly regulated in physiological conditions, they become deregulated in cancer, where MYC is oncogenically activated.

The last decade has seen MYC progress from a renowned undruggable target to a hot topic in the cancer therapy field, as proof emerged from mouse models that its inhibition constitutes an effective and broadly applicable approach to fight cancer. However, there are several aspects of MYC biology that still appear to be elusive and maintain the interest in further studying this intriguing protein. Since MYC’s discovery, more than four decades ago, multiple strategies have been developed to study it, related to the many and varied facets of its biology. This new version of The Myc gene: Methods and Protocols provides valuable tips from key “inhabitants of the MYC world,” which significantly increase the reach of our investigative tools to shed light on the mysteries still surrounding MYC.

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

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 109.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 139.99
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

Similar content being viewed by others

References

  1. Eilers M, Eisenman RN (2008) Myc’s broad reach. Genes Dev 22(20):2755–2766

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Cole MD, Henriksson M (2006) 25 years of the c-Myc oncogene. Semin Cancer Biol 16(4):241

    Article  PubMed  Google Scholar 

  3. Whitfield JR, Soucek L (2012) Tumor microenvironment: becoming sick of Myc. Cell Mol Life Sci 69(6):931–934

    Article  CAS  PubMed  Google Scholar 

  4. Dang CV (2012) MYC on the path to cancer. Cell 149(1):22–35

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Evan GI, Littlewood TD (1993) The role of c-myc in cell growth. Curr Opin Genet Dev 3(1):44–49

    Article  CAS  PubMed  Google Scholar 

  6. Hoffman B, Liebermann DA (2008) Apoptotic signaling by c-MYC. Oncogene 27(50):6462–6472

    Article  CAS  PubMed  Google Scholar 

  7. Ko A et al (2018) Oncogene-induced senescence mediated by c-Myc requires USP10 dependent deubiquitination and stabilization of p14ARF. Cell Death Differ 25(6):1050–1062

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126(4):663–676

    Article  CAS  PubMed  Google Scholar 

  9. Poli V et al (2018) MYC-driven epigenetic reprogramming favors the onset of tumorigenesis by inducing a stem cell-like state. Nat Commun 9(1):1024

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Conacci-Sorrell M et al (2014) An overview of MYC and its interactome. Cold Spring Harb Perspect Med 4(1):a014357

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. Beaulieu ME et al (2020) Structural and biophysical insights into the function of the intrinsically disordered Myc oncoprotein. Cell 9(4):1038

    Article  CAS  Google Scholar 

  12. Adhikary S, Eilers M (2005) Transcriptional regulation and transformation by Myc proteins. Nat Rev Mol Cell Biol 6(8):635–645

    Article  CAS  PubMed  Google Scholar 

  13. Brenner C et al (2005) Myc represses transcription through recruitment of DNA methyltransferase corepressor. EMBO J 24(2):336–346

    Article  CAS  PubMed  Google Scholar 

  14. Schneider A et al (1997) Association of Myc with the zinc-finger protein Miz-1 defines a novel pathway for gene regulation by Myc. Curr Top Microbiol Immunol 224:137–146

    CAS  PubMed  Google Scholar 

  15. Malynn BA et al (2000) N-myc can functionally replace c-myc in murine development, cellular growth, and differentiation. Genes Dev 14(11):1390–1399

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Fernandez PC et al (2003) Genomic targets of the human c-Myc protein. Genes Dev 17(9):1115–1129

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Shiio Y et al (2002) Quantitative proteomic analysis of Myc oncoprotein function. EMBO J 21(19):5088–5096

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Watson JD et al (2002) Identifying genes regulated in a Myc-dependent manner. J Biol Chem 277(40):36921–36930

    Article  CAS  PubMed  Google Scholar 

  19. O'Connell BC et al (2003) A large scale genetic analysis of c-Myc-regulated gene expression patterns. J Biol Chem 278(14):12563–12573

    Article  CAS  PubMed  Google Scholar 

  20. Vita M, Henriksson M (2006) The Myc oncoprotein as a therapeutic target for human cancer. Semin Cancer Biol 16(4):318–330

    Article  CAS  PubMed  Google Scholar 

  21. Murphy DJ et al (2008) Distinct thresholds govern Myc’s biological output in vivo. Cancer Cell 14(6):447–457

    Article  CAS  PubMed  Google Scholar 

  22. Meyer N, Penn LZ (2008) Reflecting on 25 years with MYC. Nat Rev Cancer 8(12):976–990

    Article  CAS  PubMed  Google Scholar 

  23. Soucek L, Evan GI (2010) The ups and downs of Myc biology. Curr Opin Genet Dev 20(1):91–95

    Article  CAS  PubMed  Google Scholar 

  24. Junttila MR, Westermarck J (2008) Mechanisms of MYC stabilization in human malignancies. Cell Cycle 7(5):592–596

    Article  CAS  PubMed  Google Scholar 

  25. Sears RC (2004) The life cycle of C-myc: from synthesis to degradation. Cell Cycle 3(9):1133–1137

    Article  CAS  PubMed  Google Scholar 

  26. Felsher DW, Bishop JM (1999) Reversible tumorigenesis by MYC in hematopoietic lineages. Mol Cell 4(2):199–207

    Article  CAS  PubMed  Google Scholar 

  27. Pelengaris S et al (2002) Suppression of Myc-induced apoptosis in beta cells exposes multiple oncogenic properties of Myc and triggers carcinogenic progression. Cell 109(3):321–334

    Article  CAS  PubMed  Google Scholar 

  28. Arvanitis C, Felsher DW (2005) Conditionally MYC: insights from novel transgenic models. Cancer Lett 226(2):95–99

    Article  CAS  PubMed  Google Scholar 

  29. Sodir NM et al (2011) Endogenous Myc maintains the tumor microenvironment. Genes Dev 25(9):907–916

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Soucek L et al (2008) Modelling Myc inhibition as a cancer therapy. Nature 455(7213):679–683

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Pelengaris S et al (1999) Reversible activation of c-Myc in skin: induction of a complex neoplastic phenotype by a single oncogenic lesion. Mol Cell 3(5):565–577

    Article  CAS  PubMed  Google Scholar 

  32. Jain M et al (2002) Sustained loss of a neoplastic phenotype by brief inactivation of MYC. Science 297(5578):102–104

    Article  CAS  PubMed  Google Scholar 

  33. Flores I et al (2004) Defining the temporal requirements for Myc in the progression and maintenance of skin neoplasia. Oncogene 23(35):5923–5930

    Article  CAS  PubMed  Google Scholar 

  34. D'Cruz CM et al (2001) c-MYC induces mammary tumorigenesis by means of a preferred pathway involving spontaneous Kras2 mutations. Nat Med 7(2):235–239

    Article  CAS  PubMed  Google Scholar 

  35. Podsypanina K et al (2008) Oncogene cooperation in tumor maintenance and tumor recurrence in mouse mammary tumors induced by Myc and mutant Kras. Proc Natl Acad Sci U S A 105(13):5242–5247

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Shachaf CM et al (2004) MYC inactivation uncovers pluripotent differentiation and tumour dormancy in hepatocellular cancer. Nature 431(7012):1112–1117

    Article  CAS  PubMed  Google Scholar 

  37. Alimova I et al (2019) Inhibition of MYC attenuates tumor cell self-renewal and promotes senescence in SMARCB1-deficient group 2 atypical teratoid rhabdoid tumors to suppress tumor growth in vivo. Int J Cancer 144(8):1983–1995

    Article  CAS  PubMed  Google Scholar 

  38. Fiorentino FP et al (2016) Growth suppression by MYC inhibition in small cell lung cancer cells with TP53 and RB1 inactivation. Oncotarget 7(21):31014–31028

    Article  PubMed  PubMed Central  Google Scholar 

  39. Annibali D et al (2014) Myc inhibition is effective against glioma and reveals a role for Myc in proficient mitosis. Nat Commun 5:4632

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Soucek L et al (2013) Inhibition of Myc family proteins eradicates KRas-driven lung cancer in mice. Genes Dev 27(5):504–513

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Savino M et al (2011) The action mechanism of the Myc inhibitor termed Omomyc may give clues on how to target Myc for cancer therapy. PLoS One 6(7):e22284

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Soucek L et al (2004) Omomyc expression in skin prevents Myc-induced papillomatosis. Cell Death Differ 11(9):1038–1045

    Article  CAS  PubMed  Google Scholar 

  43. Soucek L et al (2002) Omomyc, a potential Myc dominant negative, enhances Myc-induced apoptosis. Cancer Res 62(12):3507–3510

    CAS  PubMed  Google Scholar 

  44. Soucek L et al (1998) Design and properties of a Myc derivative that efficiently homodimerizes. Oncogene 17(19):2463–2472

    Article  CAS  PubMed  Google Scholar 

  45. Beaulieu ME et al (2019) Intrinsic cell-penetrating activity propels Omomyc from proof of concept to viable anti-MYC therapy. Sci Transl Med 11(484):eaar5012

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  46. Beaulieu ME, Soucek L (2019) Finding MYCure. Mol Cell Oncol 6(5):e1618178

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  47. Masso-Valles D, Soucek L (2020) Blocking Myc to treat Cancer: reflecting on two decades of Omomyc. Cell 9(4):883

    Article  CAS  Google Scholar 

  48. Allen-Petersen BL, Sears RC (2019) Mission possible: advances in MYC therapeutic targeting in cancer. BioDrugs 33(5):539–553

    Article  PubMed  PubMed Central  Google Scholar 

  49. Dang CV et al (2017) Drugging the ‘undruggable’ cancer targets. Nat Rev Cancer 17(8):502–508

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Whitfield JR et al (2017) Strategies to inhibit Myc and their clinical applicability. Front Cell Dev Biol 5:10

    Article  PubMed  PubMed Central  Google Scholar 

  51. Delattre P, Montagne M, Lavigne P (this volume) Methods of expression, purification, and preparation of the c-Myc b-HLH-LZ for its biophysical characterization. In: Soucek L, Whitfield J (eds) The Myc gene: methods and protocols. Springer, New York

    Google Scholar 

  52. Zinzalla G (this volume) Biophysical and structural methods to study the bHLHZip region of human c-MYC. In: Soucek L, Whitfield J (eds) The Myc gene: methods and protocols. Springer, New York

    Google Scholar 

  53. Resetca D, MacDonald AS, Kenney TMG, Wei Y, Arrowsmith CH, Raught B, Penn LZ (this volume) Identifying and validating MYC: protein interactors in pursuit of novel anti-MYC therapies. In: Soucek L, Whitfield J (eds) The Myc gene: methods and protocols. Springer, New York

    Google Scholar 

  54. Daniel CJ, Sun X-X, Chen Y, Zhang X, Dai M-S, Sears RC (this volume) Detection of posttranslational modifications on MYC. In: Soucek L, Whitfield J (eds) The Myc gene: methods and protocols. Springer, New York

    Google Scholar 

  55. Hartl M, Bister K (this volume) MYC analysis in cancer and evolution. In: Soucek L, Whitfield J (eds) The Myc gene: methods and protocols. Springer, New York

    Google Scholar 

  56. Jackstadt R, Kaller M, Menssen A, Hermeking H (this volume) Genome-wide analysis of c-MYC-regulated mRNAs and miRNAs and c-MYC DNA-binding by next-generation sequencing. In: Soucek L, Whitfield J (eds) The Myc gene: methods and protocols. Springer, New York

    Google Scholar 

  57. Cameron DP, Kuzin V, Baranello L (this volume) Analysis of Myc chromatin binding by calibrated ChIP-Seq approach. In: Soucek L, Whitfield J (eds) The Myc gene: methods and protocols. Springer, New York

    Google Scholar 

  58. Fagnocchi L, Zippo A (this volume) A high-throughput chromatin immunoprecipitation sequencing approach to study the role of MYC on the epigenetic landscape. In: Soucek L, Whitfield J (eds) The Myc gene: methods and protocols. Springer, New York

    Google Scholar 

  59. Lu D, Wilson C, Littlewood TD (this volume) Methods for determining Myc-induced apoptosis. In: Soucek L, Whitfield J (eds) The Myc gene: methods and protocols. Springer, New York

    Google Scholar 

  60. Tang H-Y, Goldman AR, Xue Z, Speicher DW, Dang CV (this volume) Measuring MYC-mediated metabolism in tumorigenesis. In: Soucek L, Whitfield J (eds) The Myc gene: methods and protocols. Springer, New York

    Google Scholar 

  61. Zhang F, Bazzar W, Alzrigat M, Larsson L-G (this volume) Methods to study Myc-regulated cellular senescence: an update. In: Soucek L, Whitfield J (eds) The Myc gene: methods and protocols. Springer, New York

    Google Scholar 

  62. Kovalski JR, Xu Y, Ruggero D (this volume) Examining Myc-dependent translation changes in cellular homeostasis and cancer. In: Soucek L, Whitfield J (eds) The Myc gene: methods and protocols. Springer, New York

    Google Scholar 

  63. Senís E, Mosteiro L, Grimm D, Abad M (this volume) A versatile in vivo system to study Myc in cell reprogramming. In: Soucek L, Whitfield J (eds) The Myc gene: methods and protocols. Springer, New York

    Google Scholar 

  64. Casacuberta-Serra S (this volume) Using flow cytometry to study Myc’s role in shaping the tumor immune microenvironment. In: Soucek L, Whitfield J (eds) The Myc gene: methods and protocols. Springer, New York

    Google Scholar 

  65. Mahauad-Fernandez WD, Rakhra K, Felsher DW (this volume) Generation of a tetracycline regulated mouse model of MYC-induced T-cell acute lymphoblastic leukemia. In: Soucek L, Whitfield J (eds) The Myc gene: methods and protocols. Springer, New York

    Google Scholar 

  66. Todorović-Raković N (this volume) Chromogenic in situ hybridization (CISH) as a method for detection of C-Myc amplification in formalin-fixed paraffin-embedded tumor tissue: an update. In: Soucek L, Whitfield J (eds) The Myc gene: methods and protocols. Springer, New York

    Google Scholar 

  67. Ogbah Z, Mancuso FM, Vivancos A (this volume) MYC copy number detection in clinical samples using a digital DNA-hybridization and detection method. In: Soucek L, Whitfield J (eds) The Myc gene: methods and protocols. Springer, New York

    Google Scholar 

  68. Burkhart CA, Haber M, Norris MD, Gudkov AV, Nikiforov MA (this volume) Cell-based methods for the identification of Myc-inhibitory small molecules. In: Soucek L, Whitfield J (eds) The Myc gene: methods and protocols. Springer, New York

    Google Scholar 

Download references

Acknowledgments

We would like to thank several funding agencies for support provided during the assembling and editing of this book, including the European Research Council (Consolidator Grant 617473), Instituto de Salud Carlos III (PI16/01224), Ministerio de Ciencia e Innovación (RTC2019-007067-1), Generalitat de Catalunya (AGAUR 2017 SGR 537), EDIReX (H2020 INFRAIA 731105-2), the Canadian Institutes of Health Research (PJT-159767), and the FERO foundation. We also acknowledge kind support from VHIO and the Cellex Foundation for providing research facilities and equipment.

Author information

Authors and Affiliations

  1. Vall d’Hebron Institute of Oncology (VHIO), Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain

    Jonathan Whitfield & Laura Soucek

  2. Peptomyc S.L., Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain

    Laura Soucek

  3. Department of Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona, Bellaterra, Spain

    Laura Soucek

  4. Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain

    Laura Soucek

Authors
  1. Jonathan Whitfield
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Laura Soucek
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jonathan Whitfield .

Editor information

Editors and Affiliations

  1. Vall d’Hebron Institute of Oncology (VHIO), Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain

    Laura Soucek

  2. Vall d’Hebron Institute of Oncology (VHIO), Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain

    Jonathan Whitfield

Rights and permissions

Reprints and permissions

Copyright information

© 2021 Springer Science+Business Media, LLC, part of Springer Nature

About this protocol

Check for updates. Verify currency and authenticity via CrossMark

Cite this protocol

Whitfield, J., Soucek, L. (2021). An “-omycs” Toolbox to Work with MYC. In: Soucek, L., Whitfield, J. (eds) The Myc Gene. Methods in Molecular Biology, vol 2318. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-1476-1_1

Download citation

  • DOI: https://doi.org/10.1007/978-1-0716-1476-1_1

  • Published:

  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-1475-4

  • Online ISBN: 978-1-0716-1476-1

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation