Pasichnyk G. Role of adaptor protein Ruk/CIN85 in the development of molecular features of tumor stem cells

The aim of the present study was to elucidate the possible role of Rukl/CIN85 in the development of CSCs' functional and molecular features on the model of MCF-7 breast adenocarcinoma cells. Stable overexpression of Rukl/CIN85 in MCF-7 cells was accompanied by increased manifestation of CSCs' characteristics such as low proliferative activity, the ability to grow independently of the substrate and to form mammoshperes under determined conditions of culturing, activation of Akt, Src, mTOR kinases and transcriptional factor NF-kB, the high number of CD44+/CD24- cells as well as the resistance to chemotherapy drugs (doxorubicin, cisplatin, etoposide and tamoxifen). Enhanced chemoresistance of Rukl/CIN85-overexpressing cells was shown to correlate with activation of aldehyde dehydrogenase enzyme, ABC transporters and increased resistance to doxorubicin-induced apoptosis. Interestingly, knocking down of Rukl/CIN85 using specific shRNA lentivirus partially reversed the observed effects of Rukl/CIN85 overexpression on MCF-7 stemness characteristics. The data obtained indicate the involvement of adaptor protein Rukl/CIN85 in the development and maintaining of stemness potential of breast adenocarcinoma MCF-7 cells.