Journal article
Redox regulation of the epigenetic landscape in Cancer: A role for metabolic reprogramming in remodeling the epigenome
Free radical biology & medicine, Vol.53(11), pp.2178-2187
12/01/2012
DOI: 10.1016/j.freeradbiomed.2012.09.028
PMCID: PMC3508253
PMID: 23022407
Abstract
Cancer arises from normal cells that acquire a series of molecular changes; however, the founding events that create the clonogens from which a tumor will arise and progress have been the subject of speculation. Through the efforts of several generations of cancer biologists it has been established that the malignant phenotype is an amalgamation of genetic and metabolic alterations. Numerous theories have suggested that either, or both, of these elements might serve as the impetus for cancer formation. Recently, the epigenetic origins of cancer have been suggested as an additional mechanism giving rise to the malignant phenotype. When the discovery that the enzymes responsible for initiating and perpetuating epigenetic events is linked to metabolism by their cofactors, a new paradigm for the origins of cancer can be created. Here, we summarize the foundation of such a paradigm on the origins of cancer, in which metabolic alterations create an epigenetic progenitor that clonally expands to become cancer. We suggest that metabolic alterations disrupt the production and availability of cofactors such as S-adenosylmethionine, α-ketoglutarate, NAD+, and acetyl-CoA to modify the epigenotype of cells. We further speculate that redox biology can change epigenetic events through oxidation of enzymes and alterations in metabolic cofactors that affect epigenetic events such as DNA methylation. Combined, these metabolic and redox changes serve as the foundation for altering the epigenotype of normal cells and creating the epigenetic progenitor of cancer.
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► Cancer is a disease associated with changes in metabolism, redox, and gene expression. ► The mechanisms leading to epigenetic alterations during carcinogenesis are unknown. ► Epigenetic disruption of cancer genes is linked to aberrant mitochondrial metabolism. ► Metabolic redox changes alter cofactor availability to enzymes that alter chromatin. ► Aberrant metabolic and redox changes cause epigenetic instability in cancer.
Details
- Title: Subtitle
- Redox regulation of the epigenetic landscape in Cancer: A role for metabolic reprogramming in remodeling the epigenome
- Creators
- Michael J Hitchler - Department of Radiation Oncology, Kaiser Permanente Los Angeles Medical Center, Los Angeles, CA 90027, USAFrederick E Domann - Department of Radiation Oncology, Free Radical and Radiation Biology Program, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA 52242, USA
- Resource Type
- Journal article
- Publication Details
- Free radical biology & medicine, Vol.53(11), pp.2178-2187
- DOI
- 10.1016/j.freeradbiomed.2012.09.028
- PMID
- 23022407
- PMCID
- PMC3508253
- NLM abbreviation
- Free Radic Biol Med
- ISSN
- 0891-5849
- eISSN
- 1873-4596
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 12/01/2012
- Academic Unit
- Pathology; Surgery; Radiation Oncology
- Record Identifier
- 9984047882802771
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