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Information × Registration Number 0225U000250, (0120U002191) , R & D reports Title Mechanisms of nuclear and metabolic reprogramming of tumor cells associated with cancer progression: contribution of adaptor protein Ruk/CIN85. popup.stage_title Механізми ядерного та метаболічного репрограмування пухлинних клітин, асоційовані з прогресією онкологічних захворювань: внесок адаптерного протеїну Ruk/CIN85. Head Drobot Liudmyla B., Доктор біологічних наук Registration Date 08-01-2025 Organization Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine popup.description1 popup.description2  Stable sublines of human lung adenocarcinoma cells A549, MOR and mouse LLC, as well as mouse melanoma B16-F10 with up/down regulation of the adaptor protein Ruk/CIN85 were obtained. Up-regulation of Ruk/CIN85 in all investigated cell sublines led to the modulation of their proliferative activity, increased migration potential and invasiveness, chemoresistance, development of CSCs features, changes in the transcriptome/metabolome in vitro, while down-regulation led to the opposite consequences and almost complete blocking metastasis in the Lewis lung carcinoma model in vivo. On the A549 and B16-F10 cell models, it was established that the production of hydrogen peroxide was positively correlated with the level of Ruk/CIN85 expression, and the inhibitor of assembly of membrane NADPH-oxidase complexes apocynin not only effectively inhibited this process, but also caused the suppression of the migratory activity of cells with up-regulation Ruk/CIN85 in vitro. In a model of 4T1 mouse breast adenocarcinoma cells with up-regulation of Ruk/CIN85, the inhibitors of lactate dehydrogenase NHI-2 and cSrc kinase PP2 in a concentration-dependent manner reduced the viability and migration rate of these cells in vitro. In the model of experimental metastasis in vivo, PP2 inhibited the metastasis of 4T1 RukUp cells with 100% efficiency by blocking their extravasation into target organs. The results of the studies performed allow us to conclude that the adaptor protein Ruk/CIN85 functions in tumor cells as a key regulator of epithelial-mesenchymal plasticity, providing reverse dynamic modulation of biological responses, phenotypic and molecular features associated with this phenomenon, depending on its expression level. Product Description popup.authors Herashchenko Denys S. Herashchenko Olha L. Horak Iryna R. Hudkova Olha O. Zhyvolozhnyi Artem Yu. Kishko Tetiana O. Krysiuk Iryna P. Latyshko Nelli V. Matyshevska Olha P. Popova Nataliia M. Skaterna Tetiana D. Tokarchuk Kateryna O. Khudiakova Olha V. popup.nrat_date 2025-01-08 Close