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Information × Registration Number 0221U101336, 0120U104156 , R & D reports Title Differential control of regulatory networks involved in the maintaining of epithelial-mesenchymal plasticity of breast adenocarcinoma cells popup.stage_title Head Drobot Liudmyla B., Доктор біологічних наук Registration Date 20-01-2021 Organization Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine popup.description2  It has been shown for the first time that adaptor protein Ruk/CIN85 can function in breast adenocarcinoma cells as one of the key regulators of epithelial-mesenchymal plasticity (EMP), providing inverse dynamic modulation of the activity of key components of signaling networks associated with EMP. The regulatory interdependence between Ruk/CIN85 and S6K1 isoforms in adenocarcinoma cells with high aggressive potential has been established. A higher level of phosphorylation of the Thr369 residue in all S6K1 isoforms (p85, p70, p60) was detected in the G4 subclone of human breast adenocarcinoma MCF-7 cells with overexpression of Ruk/CIN85, while the content of their whole forms did not differ. It has been shown that both the content and the level of p60 S6K1 activity in MCF-7 cells with up-regulation of the adaptor protein correlate with their malignant phenotype. In 4T1 cells with overexpression of Ruk/CIN85, a high content of constitutively active phosphoforms of kinases Erk1/2, mTOR, cSrc and phosphoforms of the transcription factor NF-kB was detected in comparison with the corresponding data in control cells. Similar to 4T1 cells, constitutive activation of Erk, p70 S6K, Akt, Src, mTOR kinases, NF-kB and its regulatory components were detected in MCF-7 cells with the highest expression level of the adaptor studied. According to the obtained results, the highest level of free plasminogen activator (uPA) was observed in subline of 4T1 cells with overexpression of Ruk/CIN85 (RukUp). The lowest ratio between the content of free uPA to its complex with PAI-1 among all sublines was found in RukUp cells. It was found that in MCF-7 cells, which stably overexpress Ruk/CIN85, the content of uPAR receptor is also significantly increased, compared to "mock" -transfected cells. It was also shown that in MCF-7 cells with Ruk/CIN85 overexpression, the content of vitamin D3 receptor (VDR) is significantly lower (3.3 times) compared to control cells. Product Description popup.authors Gerashchenko Olga L Horak Iryna Iryna R. Korshun Ruslan S Mazanova Anna O Yatsenko Tetiana A popup.nrat_date 2021-01-20 Close