Reach Us +1-947-333-4405
MYC, Metabolism and Malignancy: Opportunities for Therapeutic Intervention | OMICS International
ISSN: 2157-2518
Journal of Carcinogenesis & Mutagenesis

Like us on:

Make the best use of Scientific Research and information from our 700+ peer reviewed, Open Access Journals that operates with the help of 50,000+ Editorial Board Members and esteemed reviewers and 1000+ Scientific associations in Medical, Clinical, Pharmaceutical, Engineering, Technology and Management Fields.
Meet Inspiring Speakers and Experts at our 3000+ Global Conferenceseries Events with over 600+ Conferences, 1200+ Symposiums and 1200+ Workshops on
Medical, Pharma, Engineering, Science, Technology and Business

MYC, Metabolism and Malignancy: Opportunities for Therapeutic Intervention

Achuth Padmanabhan*

Department of Molecular Biophysics and Biochemistry, Yale University, USA

*Corresponding Author:
Achuth Padmanabhan
Department of Molecular Biophysics and Biochemistry
Yale University, New Haven
CT-06511, USA
E-mail: [email protected]

Received date: July 18, 2013; Accepted date: July 20, 2013; Published date: July 28, 2013

Citation: Padmanabhan A (2013) MYC, Metabolism and Malignancy: Opportunities for Therapeutic Intervention. J Carcinogene Mutagene 4:146. doi: 10.4172/2157-2518.1000146

Copyright: © 2013 Padmanabhan A. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Visit for more related articles at Journal of Carcinogenesis & Mutagenesis


Metabolic regulation in cells is hugely dependent on the availability of nutrients. Proliferation of cells requires active nutrient uptake, synthesis of nucleic acids, proteins, and lipids and production of ATP. It is thus not surprising those oncogenes that drive cell proliferation also drives metabolic regulation either directly or indirectly. One of the hallmarks of rapidly growing tumor cells is their ability to sustain high rates of glycolysis for ATP generation, irrespective of oxygen availability - a phenomenon known as the Warburg effect [1,2]. This shared property of tumor cells provides selective advantage to these cells but also opens up new opportunities for therapeutic intervention. Inhibitors of cellular proliferation that blocks or terminates DNA synthesis or that cross-links or fragments DNA have emerged as some of the classic anticancer agents. These drugs are directed toward normal cellular proliferation processes and therefore lack selectivity for neoplastic cells over proliferating normal cells. The same is true of classic inhibitors of intermediary metabolism, many of which are enzyme transition state analogues.

Since its discovery more than three decades ago as a viral oncogene (v-MYC) in the acutely transforming MC29 virus, MYC has emerged as one of the most commonly deregulated oncogene in human cancers. Apart from being frequently deregulated in many cancers, MYC appears to function downstream of most other oncogenes suggesting that MYC acts a signaling hub and a key downstream effecter. The MYC oncogene, has also been shown to play a major role in cancer cell metabolism. MYC is a basic helix-loop-helix transcription factor that forms a heterodimer with another protein called MAX, and binds DNA upstream of target genes [3]. MYC frequently accumulates in many cancers and has been shown to play a key role in tumor progression [3]. Many recent studies have revealed a strong link between MYC-dependent altered cellular metabolism and tumorigenesis [1,2]. MYC target genes include those involved in the ribosome and mitochondrial biogenesis, regulation of glucose, glutamine and nucleotide metabolism, and DNA replication [1,2]. MYC has also been shown to be involved in hypoxic adaptation. The glycolytic genes such as lactate dehydrogenase A and glutaminase are also regulated by MYC through direct and indirect mechanisms. MYC overexpression in cancers, therefore, could concurrently drive aerobic glycolysis and/or oxidative phosphorylation depending on the context of the tumor microenvironment to provide sufficient energy and anabolic substrates for cell growth and proliferation. The dependence of cancer cells on MYC to fulfill their metabolic demands and the role of MYC as a final effector in cancer cells has made it an attractive cancer therapeutic target.

Many studies have suggested that MYC inhibition can halt tumor progression, making it an interesting therapeutic target for new drug development. However, efforts to develop drugs that target MYC have largely proven unsuccessful, partly due to the lack of an obvious target-binding site on the protein. Recently, new approaches have emerged that have shown promise in selectively regulating the function on this elusive cancer target. Rapid and potent abrogation of MYC gene transcription by small molecule inhibitors of the BET family of chromatin adaptors is one such strategy. Disruption of BET bromodomain-promoter interactions leading to subsequent reduction of MYC transcript and protein levels resulted in G1 arrest and extensive apoptosis in a variety of leukemia and lymphoma cell lines [4]. Another emerging strategy is the use of a mutant basic helixloop- helix zipper domain, Omomyc, which dimerizes with MYC and sequesters it in complexes thereby preventing binding of MYC to the E-box. Thus, by acting as a potential dominant negative, Omomyc can reverse tumorigenesis in cancers driven by high-levels of MYC [5]. Small molecules such as 10058-F4, a characterized c-MYC/Max inhibitor, that’s targets the MYC/Max interaction has also been shown to lead to cell cycle arrest, apoptosis, and neuronal differentiation [6].

Since MYC acts a major regulator that controls the expression of nearly 15% of human genes there exists the concern that long-term treatment using the strategies aimed at total loss of MYC function might cause significant and uncontrollable side effects. An alternative strategy would be to use peptides and peptido-mimetics that would specifically interfere with protein-protein interaction between MYC and specific interacting proteins. Although technically challenging, if successful, this strategy would offer the advantage of specifically disrupting specific MYC function without impairing its general role in growth and metabolism. Such a strategy can also be used to fine tune MYC levels in cells. The stability of MYC in cells is regulated by various post-translational modifications. Phosphorylation at different sites influences its turnover and steady state levels [7,8]. Thus by designing peptides that would disrupt the interaction of MYC with these specific protein kinases, one could in theory regulate its turnover. This unique ability of his strategy (if successful) to fine tune MYC levels in cells as opposed to a ‘complete loss of function’ based strategy would help overcome the possible side effects of the later strategy.


Select your language of interest to view the total content in your interested language
Post your comment

Share This Article

Article Usage

  • Total views: 12058
  • [From(publication date):
    October-2013 - Dec 19, 2018]
  • Breakdown by view type
  • HTML page views : 8266
  • PDF downloads : 3792

Post your comment

captcha   Reload  Can't read the image? click here to refresh

Peer Reviewed Journals
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2018-19
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

Agri and Aquaculture Journals

Dr. Krish

[email protected]

+1-702-714-7001Extn: 9040

Biochemistry Journals

Datta A

[email protected]

1-702-714-7001Extn: 9037

Business & Management Journals


[email protected]

1-702-714-7001Extn: 9042

Chemistry Journals

Gabriel Shaw

[email protected]

1-702-714-7001Extn: 9040

Clinical Journals

Datta A

[email protected]

1-702-714-7001Extn: 9037

Engineering Journals

James Franklin

[email protected]

1-702-714-7001Extn: 9042

Food & Nutrition Journals

Katie Wilson

nutritionjourna[email protected]

1-702-714-7001Extn: 9042

General Science

Andrea Jason

[email protected]

1-702-714-7001Extn: 9043

Genetics & Molecular Biology Journals

Anna Melissa

[email protected]

1-702-714-7001Extn: 9006

Immunology & Microbiology Journals

David Gorantl

[email protected]

1-702-714-7001Extn: 9014

Materials Science Journals

Rachle Green

[email protected]

1-702-714-7001Extn: 9039

Nursing & Health Care Journals

Stephanie Skinner

[email protected]

1-702-714-7001Extn: 9039

Medical Journals

Nimmi Anna

[email protected]

1-702-714-7001Extn: 9038

Neuroscience & Psychology Journals

Nathan T

[email protected]

1-702-714-7001Extn: 9041

Pharmaceutical Sciences Journals

Ann Jose

[email protected]

1-702-714-7001Extn: 9007

Social & Political Science Journals

Steve Harry


[email protected]

1-702-714-7001Extn: 9042

© 2008- 2018 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version