THE MECHANISM OF TOLERANCE OF THE ESTROGEN-INDEPENDENT BREAST CANCER CELLS TO HYPOXIA:THE ROLE OF SNAIL1 AND BETA-CATENIN, THE EPITHELIAL-MESENCHYMAL TRANSITION PROTEINS

The main goal of the project was to study the heightened tolerance of the resistant breast cancer cells to hypoxia. Two in vitro cultured
breast cancer cell lines, the estrogen-dependent MCF-7 cells and the resistant ER-negative HBL-100 cells were used in the study.
We have demonstrated that the high expression of Snail1 (the key protein of epithelial-mesenchymal transition) is one of the factors
supporting the ER-negative breast cancer cell survival under hypoxic conditions. Snail1 produces a synergistic protective effect with betacatenin,
the transcription cofactor regulating the expression of hypoxia-dependent genes. We have established that the downregulation of
estrogen receptor activity results in Snail1 activation. The target inhibition of Snail1 signaling pathway was demonstrated to be conducive
to the increased cell sensibility to hypoxia. Thus Snail1 and its effectors may serve as perspective targets in the treatment of resistant
breast cancer.

L.B. Stefanova, A.M. Scherbakov, D.V. Sorokin, V.A. Shatskaya, M.A. Krasilnikov
Federal State Budgetary Institution «The N.N. Blokhin Russian Cancer Research Center» of the Russian Academy of Medical Sciences, Moscow, Russian Federation