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Nat Cell Biol. 2013 Jul;15(7):818-28. doi: 10.1038/ncb2774. Epub 2013 Jun 23.

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

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1
Laboratory of Molecular Biology of the Cell, CNRS UMR5239, IFR128, Ecole Normale Supérieure de Lyon, Lyon 69364, France. biroccio@ifo.it

Abstract

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.

PMID:
23792691
DOI:
10.1038/ncb2774
[Indexed for MEDLINE]
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