Periodic Reporting for period 1 - CytoTERRA (Elucidating the function of telomeric transcripts in the cytoplasm of ALT osteosarcoma cells)
Période du rapport: 2021-09-01 au 2023-08-31
The peculiar characteristic we have noticed and studied is that in ALT cancers, one molecular component typically present at chromosome ends, an RNA molecule called TERRA, is not present in the nucleus, as has been described before, but surprisingly, also outside of the nucleus, in the cytoplasm. Such an unusual observation may turn out to be important for cancer treatment or diagnosis—if we discovered that cytoplasmic TERRA (or cytoTERRA) helps the survival of ALT cancer cells, it could be attempted to target it for degradation or block its function, in other words, use it as a therapeutic target. Alternatively, cytoTERRA could turn out to be a reliable and easily detectable hallmark of ALT cancers—speeding up diagnosis and the selection of appropriate treatment regimen.
To open these possibilities, in this project, our objective was to understand what conditions drive TERRA to the cytoplasm, what are the cellular components enabling such transport and elucidate the processes in which cytoTERRA is involved.
We have introduced and discussed the acquired results with the peers in the field, through the participation in 3 scientific conferences and publication of one peer-review article, with two other manuscripts in preparation.
The results we have acquired on cytoTERRA add to the emerging picture in the field of telomere biology that TERRA, beyond its roles at chromosome ends and in the nucleus, may serve as a signaling molecule, carrying the information about telomeric DNA damage to the cytoplasm, where several lines of DNA damage response may be triggered, or even communicated to other cells. As such, cytoTERRA, or the processes it is involved in, may in the future become a diagnostically important ALT hallmark or even a therapeutic target, although the concrete applications are difficult to predict. Telomeres are viewed as an important target in cancer biology, as their successful elongation in every cell division is an acquired characteristic important for the survival of cancer cells. Besides its possible direct outcomes, the results of the cytoTERRA project thus also add to a complicated picture, where uncountable pieces of knowledge contribute to the final puzzle that is cancer molecular biology.