The Ups and Downs of Myc Biology

Overview

Journal Curr Opin Genet Dev

Publisher Elsevier

Specialties Biology
Genetics

Date 2009 Dec 8

PMID 19962879

Citations 107

Authors

Laura Soucek

Gerard I Evan

Affiliations

Soon will be listed here.

Abstract

The basic helix-loop-helix protein Myc is a renowned transcription factor controlling disparate aspects of cell physiology that, together, allow efficient proliferation of somatic cells. This ability, together with the observation that its deregulated expression occurs in the majority of human cancers, suggests that Myc could be a good therapeutic target. However, several aspects of Myc biology remain elusive: what is the major difference between oncogenic and physiological Myc? How does oncogenic Myc evade the intrinsic tumor surveillance pathways provided by evolution? If Myc inhibition were even possible, what would be the consequences for the homeostasis of normal proliferating tissues versus the fate of cancer cells? Here we summarize the latest works addressing these issues.

Citing Articles

Dynamic Multilevel Regulation of EGFR, KRAS, and MYC Oncogenes: Driving Cancer Cell Proliferation Through (Epi)Genetic and Post-Transcriptional/Translational Pathways.

Seres M, Spacayova K, Sulova Z, Spaldova J, Breier A, Pavlikova L Cancers (Basel). 2025; 17(2).

PMID: 39858030 PMC: 11763799. DOI: 10.3390/cancers17020248.

New insights into protein-protein interaction modulators in drug discovery and therapeutic advance.

Nada H, Choi Y, Kim S, Jeong K, Meanwell N, Lee K Signal Transduct Target Ther. 2024; 9(1):341.

PMID: 39638817 PMC: 11621763. DOI: 10.1038/s41392-024-02036-3.

The FGF/FGFR/c-Myc axis as a promising therapeutic target in multiple myeloma.

Giacomini A, Taranto S, Gazzaroli G, Faletti J, Capoferri D, Marcheselli R J Exp Clin Cancer Res. 2024; 43(1):294.

PMID: 39482742 PMC: 11529022. DOI: 10.1186/s13046-024-03217-2.

Exosome-mediated delivery of siRNA molecules in cancer therapy: triumphs and challenges.

Ubanako P, Mirza S, Ruff P, Penny C Front Mol Biosci. 2024; 11:1447953.

PMID: 39355533 PMC: 11442288. DOI: 10.3389/fmolb.2024.1447953.

MYC and KRAS cooperation: from historical challenges to therapeutic opportunities in cancer.

Casacuberta-Serra S, Gonzalez-Larreategui I, Capitan-Leo D, Soucek L Signal Transduct Target Ther. 2024; 9(1):205.

PMID: 39164274 PMC: 11336233. DOI: 10.1038/s41392-024-01907-z.

References

Nesbit C, Tersak J, Prochownik E . MYC oncogenes and human neoplastic disease. Oncogene. 1999; 18(19):3004-16. DOI: 10.1038/sj.onc.1202746. View

Chen Y, Blackwell T, Chen J, Gao J, Lee A, States D . Integration of genome and chromatin structure with gene expression profiles to predict c-MYC recognition site binding and function. PLoS Comput Biol. 2007; 3(4):e63. PMC: 1847699. DOI: 10.1371/journal.pcbi.0030063. View

Eisenman R . Deconstructing myc. Genes Dev. 2001; 15(16):2023-30. DOI: 10.1101/gad928101. View

Sansom O, Meniel V, Muncan V, Phesse T, Wilkins J, Reed K . Myc deletion rescues Apc deficiency in the small intestine. Nature. 2007; 446(7136):676-9. DOI: 10.1038/nature05674. View

Soucek L, Helmer-Citterich M, Sacco A, Jucker R, Cesareni G, Nasi S . Design and properties of a Myc derivative that efficiently homodimerizes. Oncogene. 1998; 17(19):2463-72. DOI: 10.1038/sj.onc.1202199. View

Bettess M, Dubois N, Murphy M, Dubey C, Roger C, Robine S . c-Myc is required for the formation of intestinal crypts but dispensable for homeostasis of the adult intestinal epithelium. Mol Cell Biol. 2005; 25(17):7868-78. PMC: 1190312. DOI: 10.1128/MCB.25.17.7868-7878.2005. View

Evan G, Harrington E, Fanidi A, Land H, Amati B, Bennett M . Integrated control of cell proliferation and cell death by the c-myc oncogene. Philos Trans R Soc Lond B Biol Sci. 1994; 345(1313):269-75. DOI: 10.1098/rstb.1994.0105. View

Muncan V, Sansom O, Tertoolen L, Phesse T, Begthel H, Sancho E . Rapid loss of intestinal crypts upon conditional deletion of the Wnt/Tcf-4 target gene c-Myc. Mol Cell Biol. 2006; 26(22):8418-26. PMC: 1636776. DOI: 10.1128/MCB.00821-06. View

Shchors K, Shchors E, Rostker F, Lawlor E, Brown-Swigart L, Evan G . The Myc-dependent angiogenic switch in tumors is mediated by interleukin 1beta. Genes Dev. 2006; 20(18):2527-38. PMC: 1578676. DOI: 10.1101/gad.1455706. View

10.

Littlewood T, Hancock D, Danielian P, Parker M, Evan G . A modified oestrogen receptor ligand-binding domain as an improved switch for the regulation of heterologous proteins. Nucleic Acids Res. 1995; 23(10):1686-90. PMC: 306922. DOI: 10.1093/nar/23.10.1686. View

11.

Jackson E, Willis N, Mercer K, Bronson R, Crowley D, Montoya R . Analysis of lung tumor initiation and progression using conditional expression of oncogenic K-ras. Genes Dev. 2001; 15(24):3243-8. PMC: 312845. DOI: 10.1101/gad.943001. View

12.

Soucek L, Jucker R, Panacchia L, Ricordy R, Tato F, Nasi S . Omomyc, a potential Myc dominant negative, enhances Myc-induced apoptosis. Cancer Res. 2002; 62(12):3507-10. View

13.

Gomez-Roman N, Grandori C, Eisenman R, White R . Direct activation of RNA polymerase III transcription by c-Myc. Nature. 2003; 421(6920):290-4. DOI: 10.1038/nature01327. View

14.

Grandori C, Cowley S, James L, Eisenman R . The Myc/Max/Mad network and the transcriptional control of cell behavior. Annu Rev Cell Dev Biol. 2000; 16:653-99. DOI: 10.1146/annurev.cellbio.16.1.653. View

15.

Lin C, Jackson A, Guo J, Linsley P, Eisenman R . Myc-regulated microRNAs attenuate embryonic stem cell differentiation. EMBO J. 2009; 28(20):3157-70. PMC: 2744176. DOI: 10.1038/emboj.2009.254. View

16.

Indra A, Warot X, Brocard J, Bornert J, Xiao J, Chambon P . Temporally-controlled site-specific mutagenesis in the basal layer of the epidermis: comparison of the recombinase activity of the tamoxifen-inducible Cre-ER(T) and Cre-ER(T2) recombinases. Nucleic Acids Res. 1999; 27(22):4324-7. PMC: 148712. DOI: 10.1093/nar/27.22.4324. View

17.

Soucek L, Whitfield J, Martins C, Finch A, Murphy D, Sodir N . Modelling Myc inhibition as a cancer therapy. Nature. 2008; 455(7213):679-83. PMC: 4485609. DOI: 10.1038/nature07260. View

18.

Takahashi K, Yamanaka S . Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006; 126(4):663-76. DOI: 10.1016/j.cell.2006.07.024. View

19.

Arnold I, Watt F . c-Myc activation in transgenic mouse epidermis results in mobilization of stem cells and differentiation of their progeny. Curr Biol. 2001; 11(8):558-68. DOI: 10.1016/s0960-9822(01)00154-3. View

20.

Evan G, Littlewood T . A matter of life and cell death. Science. 1998; 281(5381):1317-22. DOI: 10.1126/science.281.5381.1317. View