The project—CytoTERRA—aimed to understand a curious phenomenon present in ALT cancers— a subset of cancers that share a common molecular trait. In general, cancer cells achieve immortality by re-activating a particular enzyme, telomerase, that lengthens their chromosome ends (telomeres) and in this way, grants them the unlimited capacity for proliferation. ALT cancers bypass the need for the reactivation of telomerase, and they achieve immortality by recombining their chromosome ends—the short ones are then elongated using the longer ones. Cancer cells of this molecular type can be present in many tumor types, very often in cancers arising from soft tissues, such as bone cancer or certain children's brain cancers.
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.
