Adaptor protein Ruk/CIN85 modulates manifestation of cancer stem cells (CSCs) features in mouse breast adenocarcinoma 4T1 cells

TitleAdaptor protein Ruk/CIN85 modulates manifestation of cancer stem cells (CSCs) features in mouse breast adenocarcinoma 4T1 cells
Publication TypeJournal Article
Year of Publication2018
AuthorsHorak, IR, Pasichnyk, GV, Gerashchenko, DS, Knopfova, L, Borsig, L, Drobot, LB
Abbreviated Key TitleDopov. Nac. akad. nauk Ukr.
Date Published12/2018

Using mouse breast adenocarcinoma 4T1 cells with stable overexpression or knockdown of adaptor protein Ruk/CIN85, its contribution to the manifestation of cancer stem cells features was estimated. It was demonstrated that the expression levels of reprogramming factors Klf4, Pou5f1/Oct4 and Nanog, as well as CSCs surface markers Cd44 and Cd24, depended on Ruk/CIN85 expression level: increased in the case of up-regulation and decreased in the case of down-regulation. It was found that the transcriptome patterns in 4T1 subclones with different expression levels of Ruk/CIN85 correlated with their ability to form mammospheres.

Keywordsadaptor protein Ruk/CIN85, breast adenocarcinoma, cancer stem cells, reprogramming, spheroids
  1. Cojoc, M., Mäbert, K., Muders, M.H. & Dubrovska, A. (2015). A role for cancer stem cells in therapy re sistance: cellular and molecular mechanisms. Semin. Cancer Biol., 31, pp. 16-27. doi:
  2. Mani, S.A., Guo, W., Liao, M.J., Eaton, E.N., Ayyanan, A., Zhou, A.Y., Brooks, M., Reinhard, F., Zhang, C.C. & Shipitsin, M. (2008). The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell., 133, pp. 704-715. doi:
  3. Havrylov, S., Redowicz, M.J. & Buchman, V.L. (2010). Emerging roles of ruk/cin85 in vesicle-mediated transport, adhesion, migration and malignancy. Traffic, 11, pp. 721-731. doi:
  4. Cascio, S., Farkas, A.M., Hughey, R.P. & Finn, O.J. (2013). Altered glycosylation of MUC1 influences its association with CIN85: the role of this novelcomplex in cancer cell invasion and migration. Oncotarget, 4, No. 10, pp. 1686-1697. doi:
  5. Samoylenko, A., Vynnytska-Myronovska, B., Byts, N., Kozlova, N., Basaraba, O., Pasichnyk, G., Palyvoda, K., Bobak, Y., Barska, M., Mayevska, O., Rzhepetsky, Y., Shuvayeva, H., Lyzogubov, V., Usenko, V., Savran, V., Volodko, N., Buchman, V., Kietzmann, T. & Drobot, L. (2012). Increased levels of the HER1 adaptor protein Rukl/CIN85 contribute to breast cancer malignancy. Carcinogenesis, 33, pp. 1976-1984. doi:
  6. Cascio, S. & Finn, O. J. (2015). Complex of MUC1, CIN85 and Cbl in colon cancer progression and metastasis. Cancers (Basel), 7, No. 1, pp. 342-352. doi:
  7. Takahashi, K. & Yamanaka, S. (2006). Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell, 126, No. 4, pp. 663-676. doi:
  8. Yu, F., Li, J., Chen, H., Fu, J., Ray, S., Huang, S. & Ai, W. (2011). Kruppel-like factor 4 (KLF4) is required for maintenance of breast cancer stem cells and for cell migration and invasion. Oncogene, 30, No. 18, pp. 2161-2172. doi:
  9. Kim, R.-J. & Nam, J.-S. (2011). OCT4 expression enhances features of cancer stem cells in a mouse model of breast cancer. Lab. Anim. Res., 27, No. 2, pp. 147-152. doi:
  10. Lu, X., Mazur, S.J., Lin, T., Appella, E. & Xu, Y. (2014). The pluripotency factor Nanog promotes breast cancer tumorigenesis and metastasis. Oncogene, 33, No. 20, pp. 2655-2664. doi:
  11. Li, W., Ma, H., Zhang, J., Zhu, L., Wang, C. & Yang, Y. (2017). Unraveling the roles of CD44/CD24 and ALDH1 as cancer stem cell markers in tumorigenesis and metastasis. Sci. Rep., 7, 13856. doi:
  12. Pasichnyk, G.V., Povorozniuk, O.O., Horak, I.R., Gerashchenko, D.S., Ponomarenko, O.V., Samoylenko, A.A., Byts, N.V. & Drobot, L.B. (2013). Overexpression of adaptor protein Rukl/CIN85 in human breast adenocarcinoma cell line MCF-7 is accompanied by increased chemoresistance. Dopov. Nac. akad. nauk Ukr., № 12, pp. 149-156 (in Ukrainian).
  13. Ji, P., Zhang, Y., Wang, S.J., Ge, H.L., Zhao, G.P., Xu, Y.C. & Wang, Y. (2016). CD44hiCD24lo mammosphere-forming cells from primary breast cancer display resistance to multiple chemotherapeutic drugs. Oncol. Rep., 35, No. 6, pp. 3293-3302. doi:
  14. Horak, I. & Drobot, L. (2018). Adaptor protein Ruk/CIN85 modulates chemoresistance of 4T1 breast cancer cells. Ukr. Biochem. J., 90, No. 3, pp. 94-100. doi: