细胞生物学-自然2013-09-05 2:58 AM

TRF2 inhibits a cell-extrinsic pathway through which natural killer cells eliminate cancer cells : Nature Cell Biology : Nature Publishing Group

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.

KEYWORDS

SHARE & LIKE

COMMENTS

ABOUT THE AUTHOR

细胞生物学-自然

0 Following 0 Fans 0 Projects 20 Articles

SIMILAR ARTICLES

Oct4 is considered a master transcription factor for pluripotent cell self-renewal, but its biology remains poorly understood. Here, we investigated th

Read More

The transition zone is a specialized compartment found at the base of cilia, adjacent to the centriole distal end, where axonemal microtubules are heav

Read More

The adult mouse subependymal zone (SEZ) harbours adult neural stem cells (aNSCs) that give rise to neuronal and oligodendroglial progeny. However it is

Read More

Oligodendrocytes—the myelin-forming cells of the central nervous system—can be regenerated during adulthood. In adults, new oligodendrocytes originate

Read More

How different integrins that bind to the same type of extracellular matrix protein mediate specific functions is unclear. We report the functional anal

Read More

To learn more about cancer-associated fibroblasts (CAFs), we have isolated fibroblasts from different stages of breast cancer progression and analysed

Read More

The lysosomal–autophagic pathway is activated by starvation and plays an important role in both cellular clearance and lipid catabolism. However, the t

Read More

Brown adipose tissue helps to maintain body temperature in hibernators, rodents and neonatal mammals by converting lipids and glucose into heat, thereb

Read More

Fat is stored or mobilized according to food availability. Malfunction of the mechanisms that ensure this coordination underlie metabolic diseases in h

Read More

Increased stromal collagen deposition in human breast tumours correlates with metastases. We show that activation of the collagen I receptor DDR2 (disc

Read More