Metabolic defects provide a spark for the epigenetic switch in cancer

Michael J Hitchler; Frederick E Domann

doi:10.1016/j.freeradbiomed.2009.04.010

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Metabolic defects provide a spark for the epigenetic switch in cancer

Journal article

Open access

Peer reviewed

Metabolic defects provide a spark for the epigenetic switch in cancer

Michael J Hitchler and Frederick E Domann

Free radical biology & medicine, Vol.47(2), pp.115-127

07/15/2009

DOI: 10.1016/j.freeradbiomed.2009.04.010

PMCID: PMC2728018

PMID: 19362589

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http://doi.org/10.1016/j.freeradbiomed.2009.04.010View

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Abstract

Cancer is a pathology that is associated with aberrant gene expression and an altered metabolism. Whereas changes in gene expression have historically been attributed to mutations, it has become apparent that epigenetic processes also play a critical role in controlling gene expression during carcinogenesis. Global changes in epigenetic processes, including DNA methylation and histone modifications, have been observed in cancer. These epigenetic alterations can aberrantly silence or activate gene expression during the formation of cancer; however, the process leading to this epigenetic switch in cancer remains unknown. Carcinogenesis is also associated with metabolic defects that increase mitochondrially derived reactive oxygen species, create an atypical redox state, and change the fundamental means by which cells produce energy. Here, we summarize the influence of these metabolic defects on epigenetic processes. Metabolic defects affect epigenetic enzymes by limiting the availability of cofactors like S-adenosylmethionine. Increased production of reactive oxygen species alters DNA methylation and histone modifications in tumor cells by oxidizing DNMTs and HMTs or through direct oxidation of nucleotide bases. Last, the Warburg effect and increased glutamine consumption in cancer influence histone acetylation and methylation by affecting the activity of sirtuins and histone demethylases.

Neoplasms - metabolism

Oxidation-Reduction

Epigenesis, Genetic

Humans

Nucleosomes - metabolism

S-Adenosylmethionine - biosynthesis

Glutathione - biosynthesis

Animals

Neoplasms - genetics

Free Radicals - metabolism

Acetylation

Histones - metabolism

S-Adenosylmethionine - genetics

DNA Methylation - physiology

Details

Title: Subtitle: Metabolic defects provide a spark for the epigenetic switch in cancer
Creators: Michael J Hitchler - Department of Radiation Oncology, Free Radical and Radiation Biology Program, University of Iowa, Iowa City, IA 52242, USA
Frederick E Domann
Resource Type: Journal article
Publication Details: Free radical biology & medicine, Vol.47(2), pp.115-127
DOI: 10.1016/j.freeradbiomed.2009.04.010
PMID: 19362589
PMCID: PMC2728018
NLM abbreviation: Free Radic Biol Med
ISSN: 0891-5849
eISSN: 1873-4596
Publisher: United States
Grant note: R01 CA073612-10 / NCI NIH HHS R29 CA073612 / NCI NIH HHS R01 CA073612-09 / NCI NIH HHS CA11543 / NCI NIH HHS R01 CA115438 / NCI NIH HHS R56 CA073612 / NCI NIH HHS CA73612 / NCI NIH HHS R01 CA073612 / NCI NIH HHS
Language: English
Date published: 07/15/2009
Academic Unit: Pathology; Surgery; Radiation Oncology
Record Identifier: 9984047712202771

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