Trf2 influences ribosome biogenesis and global protein translation in colorectal cancer

TRF2 is a key member of the shelterin complex, directly binding to telomeric DNA, and contributing to telomere protection, T-loop stability and suppression of DNA damage response. The ability of TRF2 to bind also extra-telomeric DNA sites is well known in human cancer cells, where it is over-expressed (expecially in colon and breast cancer). A recent interactome analysis conducted in colorectal cancer cells, has further expanded TRF2 connections, revealing its unprecedented interactions with a substantial number of nucleolar proteins, suggesting potential implications for TRF2 in rRNA processing and ribosome biogenesis. Here, we explored the interactions between TRF2 and ribosomal DNA, RNA and proteins, at a molecular level, as well as TRF2 localization in the nucleolar compartments of colorectal cancer cells, which possess elevated levels of TRF2. Functionally, we analyzed the contribution of TRF2 levels in the global translational efficiency in colorectal cancer cells. Finally, in specimens from peritumoral and tumoral tissues of colorectal- cancer patients recruited for this study, we investigated the correlation between TRF2 levels and ribosomal pathway markers. In particular, we studied the mRNA and protein expression of TRF2 directly in tissue samples, and we correlated it with the expression of rRNA species, and other mRNA and proteins known as markers of translational efficiency, which are recognized as prognostic biomarkers in colon cancer progression. Our data contributes to uncovering a new role of TRF2 in the regulation of ribosome biogenesis and protein synthesis paving the way for the assessment of TRF2 as a putative biomarker for colorectal cancer progression.