Institute of Cell Biology National Academy of Sciences of Ukraine
Department of Cell Signaling
The Department of Cell Signaling conducts research aimed at increasing the efficacy and selectivity of combined antitumor metabolic therapy based on arginine starvation. In particular, the effect of arginine starvation combined with plant analogues of arginine, canavanine and indospicine, as well as mTOR and MAPK inhibitors on the proliferation and viability of diverse human tumor cells, is studied.
Indospicine has been shown for the first time to selectively impair the viability of human colorectal cancer tumor cells during arginine starvation, by integrating into newly synthesized proteins, deregulating the mTOR and MAPK signaling pathways, and causing ER stress and apoptosis. Given that this analogue is not degradated by recombinant human arginase, which is used to achieve deficit of this amino acid in vivo, indospicine is a promising component of combined metabolic therapy. It was also found that inactivation of pro-proliferative ERK and activation of proapoptotic p38 MARK may be one of the causes of antitumor effects of arginine analogues under arginine starvation. Simultaneous impact of canavanine and the autophagy inhibitor chloroquine has been shown to induce apoptotic cell death in SCOV3 ovarian carcinoma cells. It was also found for the first time that knockout of the mTOR TSC2 repressor gene increases the sensitivity of SW480 colorectal carcinoma cells to arginine starvation and sensitizes them to canavanine.
The obtained results are also the basis for studying the effectiveness of combined antitumor therapy based on arginine starvation in experimental animal models.
Thus, the main research topics of the Department are:
- Development of new approaches to anti-tumor metabolic therapy based on individual amino acid starvation.
- Study of molecular signaling mechanisms involved in the response of tumor cells to starvation of individual amino acids.
- Construction of yeast-based producers of recombinant enzymes for metabolic antitumor therapy.
- Utilization of yeast as an experimental model for the study of malignant transformation and neurodegenerative human diseases.
- Development of highly selective monoclonal antibodies for biotechnological purposes.
The Department of Cell Signaling also actively cooperates with the Faculty of Biology of Lviv Ivan Franko National University. Thus, during 2020 the Department completed 2 course works of 3rd year students, 3 diploma bachelor theses of 4th year students, 3 course works of 1st year masters, and 1 master theses of 2nd year in the specialty "091 Biology".