AI Article Synopsis
- TRF2, a protein found at the ends of chromosomes, is often overexpressed in various cancers and plays a role in tumor development, though its exact functions are still being investigated.
- Using advanced Luminex X-MAP technology, researchers found that TRF2 significantly increases the levels of VEGF-A, which is important for blood vessel formation (angiogenesis) in cancer cells, independently of its known role in protecting telomeres.
- The study also identified that TRF2 enhances the expression of SULF2, which modifies the connection of VEGF-A to the cell surface, and found that high levels of TRF2 and SULF2 are linked to worse outcomes for patients with colorectal cancer.
Article Abstract
The telomeric protein TRF2 is overexpressed in several human malignancies and contributes to tumorigenesis even though the molecular mechanism is not completely understood. By using a high-throughput approach based on the multiplexed Luminex X-MAP technology, we demonstrated that TRF2 dramatically affects VEGF-A level in the secretome of cancer cells, promoting endothelial cell-differentiation and angiogenesis. The pro-angiogenic effect of TRF2 is independent from its role in telomere capping. Instead, TRF2 binding to a distal regulatory element promotes the expression of SULF2, an endoglucosamine-6-sulfatase that impairs the VEGF-A association to the plasma membrane by inducing post-synthetic modification of heparan sulfate proteoglycans (HSPGs). Finally, we addressed the clinical relevance of our findings showing that TRF2/SULF2 expression is a worse prognostic biomarker in colorectal cancer (CRC) patients.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6468246 | PMC |
| http://dx.doi.org/10.1093/nar/gkz041 | DOI Listing |
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