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
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
收藏
页码:818 / +
页数:22
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