Abstract |
Ten-eleven translocation enzymes (TET1, TET2, and TET3), which induce DNA demethylation and gene regulation by converting 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), are often down-regulated in cancer. We uncover, in basal-like breast cancer (BLBC), genome-wide 5hmC changes related to TET1 regulation. We further demonstrate that TET1 repression is associated with high expression of immune markers and high infiltration by immune cells. We identify in BLBC tissues an anticorrelation between TET1 expression and the major immunoregulator family nuclear factor κB (NF-κB). In vitro and in mice, TET1 is down-regulated in breast cancer cells upon NF-κB activation through binding of p65 to its consensus sequence in the TET1 promoter. We lastly show that these findings extend to other cancer types, including melanoma, lung, and thyroid cancers. Together, our data suggest a novel mode of regulation for TET1 in cancer and highlight a new paradigm in which the immune system can influence cancer cell epigenetics.
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Authors | Evelyne Collignon, Annalisa Canale, Clémence Al Wardi, Martin Bizet, Emilie Calonne, Sarah Dedeurwaerder, Soizic Garaud, Céline Naveaux, Whitney Barham, Andrew Wilson, Sophie Bouchat, Pascale Hubert, Carine Van Lint, Fiona Yull, Christos Sotiriou, Karen Willard-Gallo, Agnès Noel, François Fuks |
Journal | Science advances
(Sci Adv)
Vol. 4
Issue 6
Pg. eaap7309
(06 2018)
ISSN: 2375-2548 [Electronic] United States |
PMID | 29938218
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Biomarkers
- NF-kappa B
- Proto-Oncogene Proteins
- Mixed Function Oxygenases
- TET1 protein, human
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Topics |
- Adaptive Immunity
- Biomarkers
- DNA Methylation
- Epigenesis, Genetic
- Gene Expression Profiling
- Gene Expression Regulation, Neoplastic
- Humans
- Immunity
- Immunity, Innate
- Mixed Function Oxygenases
(genetics)
- NF-kappa B
(metabolism)
- Neoplasms
(etiology, metabolism, pathology)
- Neoplasms, Basal Cell
(etiology, metabolism, pathology)
- Promoter Regions, Genetic
- Protein Binding
- Proto-Oncogene Proteins
(genetics)
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