Immunity drives TET1 regulation in cancer through NF-κB

被引：74

作者：

Collignon, Evelyne ^{[1
,2
]}

Canale, Annalisa

Al Wardi, Clemence ^{[1
]}

Bizet, Martin ^{[1
]}

Calonne, Emilie ^{[1
]}

Dedeurwaerder, Sarah ^{[1
]}

Garaud, Soizic ^{[3
]}

Naveaux, Celine ^{[3
]}

Barham, Whitney ^{[4
]}

Wilson, Andrew ^{[4
]}

Bouchat, Sophie ^{[5
]}

Hubert, Pascale ^{[6
]}

Van Lint, Carine ^{[5
]}

Yull, Fiona ^{[4
]}

Sotiriou, Christos ^{[7
]}

Willard-Gallo, Karen ^{[3
]}

Noel, Agnes ^{[2
]}

Fuks, Francois ^{[1
]}

机构：

[1] ULB, Fac Med, Cancer Res Ctr U CRC, Lab Canc Epigenet, Brussels, Belgium

[2] Univ Liege, Lab Tumor & Dev Biol, Grp Interdisciplinaire Genoprote Appl GIGA Canc, Liege, Belgium

[3] ULB, Inst Jules Bordet, Mol Immunol Unit, Brussels, Belgium

[4] Vanderbilt Univ, Vanderbilt Ingram Canc Ctr, Dept Canc Biol, Nashville, TN 37232 USA

[5] ULB, U CRC, Serv Mol Virol, Dept Mol Biol, Gosselies, Belgium

[6] Univ Liege, GIGA Canc, Lab Expt Pathol, Liege, Belgium

[7] ULB, Inst Jules Bordet, Breast Canc Translat Res Lab, Brussels, Belgium

来源：

SCIENCE ADVANCES | 2018年 / 4卷 / 06期

关键词：

BREAST-CANCER; GENE-EXPRESSION; DNA DEMETHYLATION; 5-HYDROXYMETHYLCYTOSINE; PROLIFERATION; ACTIVATION; METHYLATION; GROWTH; CELLS; TRANSCRIPTION;

D O I：

10.1126/sciadv.aap7309

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 immuno-regulator family nuclear factor kappa B (NF-kappa B). In vitro and in mice, TET1 is down-regulated in breast cancer cells upon NF-kappa B 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.

引用

页数：14

共 81 条

[1] The p65 (RelA) subunit of NF-κB interacts with the histone deacetylase (HDAC) corepressors HDAC1 and HDAC2 to negatively regulate gene expression [J].