A group of researchers at the MedUni Vienna has now identified a new mechanism by which telomerase is induced. This mechanism involves a retrotransposon that has previously been considered more or less superfluous and referred to as “junk DNA”. These findings could provide new approaches to cancer treatment.
Normal cells have an internal clock built in that determines how long they live. This inner clock is formed by telomeres. These structures are repetitive DNA sequences at the ends of chromosomes. Telomeres shorten during cell division. If telomeres become critically short, the cell dies the natural cell death.
Tumour cells, however, have developed mechanisms that counteract the telomere shortening process and therefore cell aging. They do this mainly by activating the enzyme telomerase, which can extend telomeres. Telomerase is otherwise only active in stem cells and during embryonic development.
A group of researchers (led by Michael Bergmann) at the MedUni Vienna’s University Department of Surgery has now identified a new mechanism by which telomerase is activated in tumour cells.
Researchers have discovered that human telomerase can be induced (initiated / activated) in all kinds of tumour cells by the retrotransposon Line-1. Line-1-coding sequences account for 17 per cent of the human genome and are usually regarded as “junk DNA”, i.e. relatively non-functional DNA. Less than 1 in 1,000 of these sequences actually codes for active proteins.
Retrotransposons can jump within chromosomal DNA (in other words, integrate themselves in a new location on activation) and therefore carry the potential to change the genome. Since Line-1 is physiologically active in embryonic development, these sequences have to date merely been attributed a certain degree of evolutionary potential.
In this study, Line-1 has therefore been attributed for the first time with a new function in the domain of telomere regulation / cell aging. Alongside this telomere regulation, it was also possible to demonstrate that Line-1 also induces stem cell-associated genes such as KLF-4 and c-myc. “Both mechanisms, the induction of human telomerase and the induction of stem cell factors, now also explain the negative prognostic effect of Line-1 in tumour cells. This makes Line-1 a potential new target in cancer therapy,” explains study leader Michael Bergmann.
The project was carried out as part of Thomas Aschacher’s PhD dissertation, supervised by Michael Bergmann in the surgical research laboratory of the University Department of Surgery, with overhead funding coming from other grants and pharmacy funds. The technical support for the project came from the working group led by Klaus Holzmann (Institute of Cancer Research) within the Vienna Comprehensive Cancer Center.
LINE-1 induces hTERT and ensures telomere maintenance in tumour cell lines, T Aschacher, B Wolf, F Enzmann, P Kienzl, B Messner, S Sampl, M Svoboda, D Mechtcheriakova, K Holzmann, M Bergmann