TRF2 inhibits a cell-extrinsic pathway through which natural killer cells eliminate cancer cells

被引：102

作者：

Biroccio, Annamaria ^{[1
,2
]}

Cherfils-Vicini, Julien ^{[3
]}

Augereau, Adeline ^{[1
,3
]}

Pinte, Sebastien ^{[1
]}

Bauwens, Serge ^{[1
]}

Ye, Jing ^{[1
,3
,4
]}

Simonet, Thomas ^{[1
]}

Horard, Beatrice ^{[1
]}

Jamet, Karine ^{[3
]}

Cervera, Ludovic ^{[3
]}

Mendez-Bermudez, Aaron ^{[3
]}

Poncet, Delphine ^{[1
]}

Grataroli, Renee ^{[1
]}

de Rodenbeeke, Claire T'kint ^{[1
]}

Salvati, Erica ^{[2
]}

Rizzo, Angela ^{[2
]}

Zizza, Pasquale ^{[2
]}

Ricoul, Michelle ^{[5
]}

Cognet, Celine ^{[6
,7
]}

Kuilman, Thomas ^{[8
]}

Duret, Helene ^{[9
]}

Lepinasse, Florian ^{[10
,11
]}

Marvel, Jacqueline ^{[12
]}

Verhoeyen, Els ^{[13
]}

Cosset, Francois-Loic ^{[13
]}

Peeper, Daniel ^{[8
]}

Smyth, Mark J. ^{[9
,14
]}

Londono-Vallejo, Arturo ^{[15
]}

Sabatier, Laure ^{[15
]}

Picco, Vincent ^{[3
]}

Pages, Gilles ^{[3
]}

Scoazec, Jean-Yves ^{[10
,11
]}

Stoppacciaro, Antonella ^{[16
]}

Leonetti, Carlo ^{[2
]}

Vivier, Eric ^{[6
,7
]}

Gilson, Eric ^{[1
,3
,17
]}

机构：

[1] Ecole Normale Super Lyon, CNRS, UMR5239, Lab Mol Biol Cell,IFR128, F-69364 Lyon, France

[2] Regina Elena Inst Canc Res, I-00158 Rome, Italy

[3] Univ Nice, CNRS, UMR7284, INSERM,U1081,IRCAN,Fac Med, F-06107 Nice, France

[4] Shanghai Jiao Tong Univ, Shanghai Ruijin Hosp, Shanghai 200025, Peoples R China

[5] Commissariat Energie Atom, DSV Radiobiol & Oncol Unit, F-92265 Fontenay Aux Roses, France

[6] Aix Marseille Univ, Ctr Immunol Marseille Luminy, INSERM, UM2,UMR1104,CNRS,UMR7280, F-13288 Marseille, France

[7] Hop Conception, Assistance Publ Hop Marseille, F-13005 Marseille, France

[8] Netherlands Canc Inst, Div Mol Genet, NL-1066 CX Amsterdam, Netherlands

[9] Peter MacCallum Canc Ctr, Canc Immunol Program, East Melbourne, Vic 3002, Australia

[10] Hop Edouard Herriot, Hosp Civils Lyon, Serv Anat Patol, F-69437 Lyon 03, France

[11] Fac Laennec, INSERM, UMR1052, F-69372 Lyon 08, France

[12] Univ Lyon 1, INSERM, U851, IFR128, F-69366 Lyon, France

[13] Ecole Normale Super Lyon, INSERM, U758, F-69364 Lyon 07, France

[14] Queensland Inst Med Res, Herston, Qld 4006, Australia

[15] UPMC, Inst Curie, CNRS, UMR3244, F-75248 Paris, France

[16] II Fac, Expt Med & Pathol Dept, I-00189 Rome, Italy

[17] CHU Nice, Archet Hosp 2, Dept Med Genet, F-06202 Nice 3, France

来源：

NATURE CELL BIOLOGY | 2013年 / 15卷 / 07期

基金：

英国医学研究理事会;

关键词：

HEPARAN-SULFATE PROTEOGLYCANS; TELOMERE DYSFUNCTION; DAMAGE RESPONSE; UP-REGULATION; IN-VIVO; ATM; EXPRESSION; END; PROTECTION; PROTEINS;

D O I：

10.1038/ncb2774

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

Dysfunctional telomeres suppress tumour progression by activating cell-intrinsic programs that lead to growth arrest. Increased levels of TRF2, a key factor in telomere protection, are observed in various human malignancies and contribute to oncogenesis. We demonstrate here that a high level of TRF2 in tumour cells decreased their ability to recruit and activate natural killer (NK) cells. Conversely, a reduced dose of TRF2 enabled tumour cells to be more easily eliminated by NK cells. Consistent with these results, a progressive upregulation of TRF2 correlated with decreased NK cell density during the early development of human colon cancer. By screening for TRF2-bound genes, we found that HS3ST4-a gene encoding for the heparan sulphate (glucosamine) 3-O-sulphotransferase 4-was regulated by TRF2 and inhibited the recruitment of NK cells in an epistatic relationship with TRF2. Overall, these results reveal a TRF2-dependent pathway that is tumour-cell extrinsic and regulates NK cell immunity.

引用

页码：818 / +

页数：22

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