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Fiona Yull

Last active: 3/31/2020

Immunity drives regulation in cancer through NF-κB.

Collignon E, Canale A, Al Wardi C, Bizet M, Calonne E, Dedeurwaerder S, Garaud S, Naveaux C, Barham W, Wilson A, Bouchat S, Hubert P, Van Lint C, Yull F, Sotiriou C, Willard-Gallo K, Noel A, Fuks F
Sci Adv. 2018 4 (6): eaap7309

PMID: 29938218 · PMCID: PMC6010319 · DOI:10.1126/sciadv.aap7309

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 regulation. We further demonstrate that repression is associated with high expression of immune markers and high infiltration by immune cells. We identify in BLBC tissues an anticorrelation between expression and the major immunoregulator family nuclear factor κB (NF-κB). In vitro and in mice, is down-regulated in breast cancer cells upon NF-κB activation through binding of p65 to its consensus sequence in the 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 in cancer and highlight a new paradigm in which the immune system can influence cancer cell epigenetics.

MeSH Terms (16)

Adaptive Immunity Biomarkers DNA Methylation Epigenesis, Genetic Gene Expression Profiling Gene Expression Regulation, Neoplastic Humans Immunity Immunity, Innate Mixed Function Oxygenases Neoplasms Neoplasms, Basal Cell NF-kappa B Promoter Regions, Genetic Protein Binding Proto-Oncogene Proteins

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