MYC, metabolism, and cancer

Zachary E. Stine, Zandra E. Walton, Brian J. Altman, Annie L. Hsieh, Chi V. Dang

Research output: Contribution to journalArticle

Abstract

The MYC oncogene encodes a transcription factor, MYC, whose broad effects make its precise oncogenic role enigmatically elusive. The evidence to date suggests that MYC triggers selective gene expression amplification to promote cell growth and proliferation. Through its targets, MYC coordinates nutrient acquisition to produce ATP and key cellular building blocks that increase cell mass and trigger DNA replication and cell division. In cancer, genetic and epigenetic derangements silence checkpoints and unleash MYC’s cell growth- and proliferation-promoting metabolic activities. Unbridled growth in response to deregulated MYC expression creates dependence on MYC-driven metabolic pathways, such that reliance on specific metabolic enzymes provides novel targets for cancer therapy. Significance: MYC’s expression and activity are tightly regulated in normal cells by multiple mechanisms, including a dependence upon growth factor stimulation and replete nutrient status. In cancer, genetic deregulation of MYC expression and loss of checkpoint components, such as TP53, permit MYC to drive malignant transformation. However, because of the reliance of MYC-driven cancers on specific metabolic pathways, synthetic lethal interactions between MYC overexpression and specific enzyme inhibitors provide novel cancer therapeutic opportunities.

Original languageEnglish (US)
Pages (from-to)1024-1039
Number of pages16
JournalCancer Discovery
Volume5
Issue number10
DOIs
StatePublished - Oct 1 2015
Externally publishedYes

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Neoplasms
Metabolic Networks and Pathways
Growth
Cell Proliferation
Gene Amplification
Enzyme Inhibitors
DNA Replication
Oncogenes
Epigenomics
Cell Division
Intercellular Signaling Peptides and Proteins
Transcription Factors
Adenosine Triphosphate
Gene Expression
Food
Enzymes
Therapeutics

ASJC Scopus subject areas

  • Oncology

Cite this

Stine, Z. E., Walton, Z. E., Altman, B. J., Hsieh, A. L., & Dang, C. V. (2015). MYC, metabolism, and cancer. Cancer Discovery, 5(10), 1024-1039. https://doi.org/10.1158/2159-8290.CD-15-0507

MYC, metabolism, and cancer. / Stine, Zachary E.; Walton, Zandra E.; Altman, Brian J.; Hsieh, Annie L.; Dang, Chi V.

In: Cancer Discovery, Vol. 5, No. 10, 01.10.2015, p. 1024-1039.

Research output: Contribution to journalArticle

Stine, ZE, Walton, ZE, Altman, BJ, Hsieh, AL & Dang, CV 2015, 'MYC, metabolism, and cancer', Cancer Discovery, vol. 5, no. 10, pp. 1024-1039. https://doi.org/10.1158/2159-8290.CD-15-0507
Stine ZE, Walton ZE, Altman BJ, Hsieh AL, Dang CV. MYC, metabolism, and cancer. Cancer Discovery. 2015 Oct 1;5(10):1024-1039. https://doi.org/10.1158/2159-8290.CD-15-0507
Stine, Zachary E. ; Walton, Zandra E. ; Altman, Brian J. ; Hsieh, Annie L. ; Dang, Chi V. / MYC, metabolism, and cancer. In: Cancer Discovery. 2015 ; Vol. 5, No. 10. pp. 1024-1039.
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