While stem cells and tumor cells are immortal, all other cells in our body slowly die. The reason for this is that the DNA strand becomes slightly shorter each time a cell divides. At some point, this shortening makes it too risky for the cell to divide and it dies. The key to this lies in telomerase, also known as the "infinity enzyme", whose discoverers were awarded the Nobel Prize for Medicine in 2009. The enzyme telomerase forms a kind of protective cap at the end of the DNA strands, which is activated in stem and tumor cells and protects the DNA from shortening during cell division (replication). This ensures that reproducibility is fully maintained. Normal cells do not produce enough telomerase, the protective caps become shorter and shorter and cell growth is halted.
TERRA blocks infinity enzyme
In this study, 68 patients with colorectal cancer (CRC) were examined for correlations between telomere biology, transcripts of genes for growth and progressive "spreading" through cancer metastasis and the course of the disease. The result: the transcript TERRA (telomere repeat-containing RNA) is produced less in the tumors than in the surrounding healthy tissue. In the tumor model with artificially increased production of TERRA, tumor growth is significantly reduced. TERRA and the telomerase RNA component (TERC) regulate telomerase activity and thus contribute to telomere equilibrium (homeostasis) by influencing telomere length and the immortality characteristic of cancer cells. TERRA can thus prevent telomerase from being active in tumor cells and causing tumor cell immortality. This is possible because telomerase itself has an RNA as an enzyme component that is blocked by TERRA.
Collaboration with international experts on the immortality of tumor cells
This study was initiated under the direction of scientist Klaus Holzmann, Medical University of Vienna, Comprehensive Cancer Center Vienna, Center for Cancer Research, together with surgeon Stefan Stättner, Klinik Favoriten, on patients diagnosed with colon cancer. Most of the data was collected and analyzed over an extended period at the Medical University of Vienna. With the help of national clinicians and colleagues (Tamara Braunschmid, Brigitte Marian, Wolfgang Mikulits) and in cooperation with international experts (Roger Reddel, Jeremy Henson and Loretta Lau from Australia, Sarantis Gagos from Greece), leaders in the research field of tumor cell immortality, this extensive study was completed and published.
Outlook
The data from the study will enable further, more complex research with the aim of investigating the formation of transcripts and the interaction of different cell types in the tumor in order to clarify the mechanism of action. In further studies, these potential new therapeutics could be evaluated and made available to patients with colon cancer.
Publication: Cellular Oncology
Title: Telomere transcripts act as tumor suppressor and are associated with favorable prognosis in colorectal cancer with low proliferating cell nuclear antigen expression
Authors: Philip Kienzl, Abigail J. Deloria, Monika Hunjadi, Juliane M. Hadolt, Max-Felix Haering, Angrit Bothien, Doris Mejri, Medina Korkut-Demirbaş, Sandra Sampl, Gerhard Weber, Christine Pirker, Severin Laengle, Tamara Braunschmid, Eleni Dragona, Brigitte Marian, Sarantis Gagos, Lingeng Lu, Jeremy D.Henson, Loretta M. S. Lau, Roger R. Reddel, Wolfgang Mikulits, Stefan Stättner & Klaus Holzmann
doi: 10.1007/s13402-024-00986-y