Duration of the project
01.02.2024. - 31.10.2024.
Countries and institutions involved in the project



Project manager
Prof. Dr. Reet Kurg
Short description of the achieved project aim(s)
The process how cancer cells can escape lethality after cancer therapy and cause cancer relapse is subject of modern research. Cancer cells treated by radio-chemical approaches obtain many damages in the DNA that may result in a loss of its regulatory stability. By this way cells can be driven into senescence (i.e. an inactive, not-proliferating arrest state) from which they can escape, reprogram their activities and develop into a proliferating, clonogenic, survival state. The aim of the project was a contribution to a better understanding of this process.
We have used an established embryonal ovarian carcinoma cell model (cell line PA-1) to investigate the fluctuation of cells between senescence (cells may finally die) and self-renewal escape-state after treatment with the chemotherapy medication etoposide. By flow cytometry, we followed the change of epigenetic landscape (especially the antagonist Oct4 and p21) within ten days after etoposide treatment and showed that days 4 to 6 were critical for the cell fate, i.e. the survival of cells as senescent or proliferating. These epigenetic fluctuations were accompanied by changes in euchromatin (EC) and heterochromatin (HC) organization patterns that were detected and quantified by confocal as well as super-resolution single molecule localization microscopy (SMLM). The data were compatible with the following outcome: On day 3 after etoposide treatment EC and HC were less organized and more relaxed indicating a better accessibility and increased EC activity. On day 5 an entity of cells showed a more organized HC with condensed clusters. Also clustering EC indicated a reduced and more directed genomic activity. The fluctuation process of chromatin was accompanied by the secretion of nanovesicles to the extracellular environment. In conclusion, our data suggest that this is the decision point whether cells remain into senescence (and finally die) or escape senescence and survive proliferating after chemotherapy treatment.
Direct and indirect target group of the project
Direct: senior scientists, PhD students, master students, bachelor students involved in the research and measurements
Indirect: scientists informed by publication of results, students and participants of the symposium