Abstract
The mechanisms governing the methylome profile of tumor suppressors and oncogenes have expanded with the discovery of oxidized states of 5-methylcytosine (5mC). Ten-eleven translocation (TET) enzymes are a family of dioxygenases that iteratively catalyze 5mC oxidation and promote cytosine demethylation, thereby creating a dynamic global and local methylation landscape. While the catalytic function of TET enzymes during stem cell differentiation and development have been well studied, less is known about the multifaceted roles of TET enzymes during carcinogenesis. This review outlines several tiers of TET regulation and overviews how TET deregulation promotes a cancer phenotype. Defining the tissue-specific and context-dependent roles of TET enzymes will deepen our understanding of the epigenetic perturbations that promote or inhibit carcinogenesis.
Keywords:
5-hydroxymethylcytosine; carcinogenesis; epigenetics; ten-eleven translocation.
Published by Elsevier Inc.
Publication types
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Research Support, N.I.H., Extramural
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Review
MeSH terms
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5-Methylcytosine / metabolism
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Antineoplastic Combined Chemotherapy Protocols / pharmacology
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Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
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Carcinogenesis / genetics
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Carcinogenesis / immunology
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Carcinogenesis / pathology
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Clinical Trials as Topic
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DNA Methylation / drug effects
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DNA Methylation / immunology
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DNA-Binding Proteins / antagonists & inhibitors
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Dioxygenases / antagonists & inhibitors
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Dioxygenases / genetics
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Dioxygenases / metabolism*
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Drug Synergism
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Epigenesis, Genetic / drug effects
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Epigenesis, Genetic / immunology
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Gene Expression Regulation, Neoplastic / drug effects
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Gene Expression Regulation, Neoplastic / immunology
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Humans
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Immune Checkpoint Inhibitors / pharmacology
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Immune Checkpoint Inhibitors / therapeutic use
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Mixed Function Oxygenases / antagonists & inhibitors
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Mixed Function Oxygenases / genetics
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Mixed Function Oxygenases / metabolism*
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Mutation
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Neoplasms / drug therapy
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Neoplasms / genetics*
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Neoplasms / immunology
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Neoplasms / pathology
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Proto-Oncogene Proteins / antagonists & inhibitors
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / metabolism*
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Treatment Outcome
Substances
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DNA-Binding Proteins
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Immune Checkpoint Inhibitors
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Proto-Oncogene Proteins
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5-Methylcytosine
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Mixed Function Oxygenases
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TET1 protein, human
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TET3 protein, human
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Dioxygenases
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TET2 protein, human