Article (Scientific journals)
Immunity drives TET1 regulation in cancer through NF-kappaB.
Collignon, Evelyne; Canale, Annalisa; Al Wardi, Clemence et al.
2018In Science Advances, 4 (6), p. 7309
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Abstract :
[en] 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 kappaB (NF-kappaB). In vitro and in mice, TET1 is down-regulated in breast cancer cells upon NF-kappaB 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.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Collignon, Evelyne 
Canale, Annalisa  ;  Université de Liège - ULiège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement
Al Wardi, Clemence
Bizet, Martin
Calonne, Emilie
Dedeurwaerder, Sarah
Garaud, Soizic
Naveaux, Celine
Barham, Whitney
Wilson, Andrew
Bouchat, Sophie
Hubert, Pascale  ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques
Van Lint, Carine
Yull, Fiona
Sotiriou, Christos
Willard-Gallo, Karen
Noël, Agnès  ;  Université de Liège - ULiège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement
Fuks, F 
More authors (8 more) Less
 These authors have contributed equally to this work.
Language :
English
Title :
Immunity drives TET1 regulation in cancer through NF-kappaB.
Publication date :
2018
Journal title :
Science Advances
eISSN :
2375-2548
Publisher :
American Association for the Advancement of Science (AAAS), United States
Volume :
4
Issue :
6
Pages :
eaap7309
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 19 September 2018

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