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Registration Number

0215U003382, 0110U002698 , R & D reports

Title

Mechanisms underlying regulation of biological responses of normal and transformed cells by adaptor/scaffold protein Ruk/CIN85

Head

Drobot L.B.,

Registration Date

28-01-2015

Organization

A.V.Palladin Institute of Biochemistry of National Academy of Sciences

Description

In the present study both the phosphorylation of Ruk/CIN85 protein and changes in the level of its phosphorylation in the course of cellular biological responses were established. The data obtained can suggest the functional role of Ruk/CIN85-PKD interaction in regulation of cell migration and invasion. It was demonstrated the increased level of uPA and of uPAR receptor expression as well modulation of uPA-dependent proliferation in cells with overexpression of Ruk/CIN85, followed by further increase under hypoxia conditions. In contrast to this, Ruk/CIN85 expression in human breast adenocarcinoma MCF-7 cells does not change under mild hypoxia conditions, and increases under insulin and insulin-like growth factor 1 action. Moreover, IGF-1 exhibits more potent stimulation of Ruk/CIN85 overexpressing MCF-7 cells proliferation than of control cells. Neither Ruk/CIN85 expression induction nor increased proliferative activity of MCF-7 cells were observed in the presence of PI3K/Akt signal pathway inhibitor LY294002. We show that the shRNA-mediated decrease of Ruk/CIN85 level in mouse Lewis lung carcinoma LLC cells leads to increased in vitro proliferative activity by aproximately 30%, enhanced tumor growth following a short latency, 30% increase in tumor volume and mass and double metastasis number in vivo. Using immunohistochemistry, the increased level of Ruk/CIN85 expression in human lung adenocarcinoma samples was demonstrated. These results confirm that Ruk/CIN85 adaptor protein is not just involved in regulation of normal cellular homeostasis, but may also play a major role in carcinogenesis.

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Биць Н.В.
Пасічник Г.В.
Петухов Д.М.
Самойленко А.А.