Work

The mortality caused by different kinds of cancers takes a second place in the world after death from cardiovascular disorders. Over the past decade in Ukraine the number of patients with diagnosed cancer was increased for more than 25%, moreover, around 35% of deaths were people at the age of 25-50 years. That is why one of the most important tasks in current biomedical research is the identification of key factors, which play a critical role in the progression of different kinds of tumors, and therefore can be effective diagnostic and prognostic markers in cancer therapy. A number of malignancies is well characterized by the impaired functioning of mTOR/PI3K cellular signaling pathways and its key components, namely mammalian target of rapamycin (mTOR, which is overactivated in the breast tumors and thyroid glands, prostate); kinases of S6 ribosomal protein (S6K1 and S6K2, with the increased expression in the breast tumors); and chitinase 3-like protein 1 (CHI3L1, which demonstrates a high level of expression in brain tumors). Current project includes a series of publications, which describe the identification and characteristics of new isoforms of mTOR kinase, as well as role its role in the regulation of proliferation and locomotor properties of malignant cells. Moreover, the interaction of S6K with a new partner protein TDRD7 has been described. Additionally, authors demonstrate the positive effect of a stable production of CHI3L1 on the activation of MAPK/PI3K/mTOR key compounds. Thus, expression of CHI3L1 leads to the phosphorylation of ERK1/2 with respective subcellular localization and has an impact on the malignant properties of cells, such as proliferation and substrate-independent growth. Also, it was shown that the intracranial implantation of cells that stably produce CHI3L1 into the brain of immunocompetent rats results in the formation of malignant tumors. Besides of the fundamental importance, obtained results might be used in a number of applied applications as well. Particularly, during the work number of monoclonal antibodies against S6K2, TDRD7 and Ki67 was obtained and characterized, which allow to use them in a further research (i.e, design of diagnostic test kits). Also a new approach of glioblastoma subtyping has been developed as well as a new model of the brain tumor that can be used for the testing of anticancer drugs was proposed. All results submitted in current application are described in 86 publications, 17 research papers in prereview journals (with a total impact factor 18,733) and 69 thesis at the national and international conferences. H-indexes of co-authors are 3, 3, 1 and 2, respectively.