Biopolym. Cell. 2023; 39(3):189-200.
http://dx.doi.org/10.7124/bc.000A9D
Structure and Function of Biopolymers
Alterations in S6K1 isoforms expression induce Epithelial to Mesenchymal Transition and Estrogen Receptor 1 Silencing in human breast adenocarcinoma MCF-7 cells
1Garifulin O. M., 1Zaiets I. V., 1Kosach V. R., 2Horak I. R., 1Khoruzhenko A. I., 1Gotsulyak N. Ya., 1Savinska L. O., 1Kroupskaya I. V., 1Martsynyuk M. Ye., 2Drobot L. B., 1Filonenko V. V.
  1. Institute of Molecular Biology and Genetics, NAS of Ukraine
    150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03143
  2. Palladin Institute of Biochemistry, NAS of Ukraine
    9, Leontovycha Str., Kyiv, Ukraine, 01054

Abstract

Aim. To evaluate an impact of different S6K1 isoforms expression in MCF7 cells on initiation of Epithelial to Mesenchymal Transition (EMT). Methods. Immunocytochemical analysis, Real-Time PCR, Western blot. Results. We have demonstrated that unbalanced expression of p60, p70 and p85-S6K1 isoforms in MCF-7, namely downregulation of p70 and p85, and basal p60 expression, mediated by the CRISPR-Cas9 gene editing resulted in altered morphology and increased cell motility. Such changes were associated with the expression of genes whose products are involved in the regulation of cell motility, interaction with the extracellular matrix and loss of cellular adhesion demonstrating their increased potential for invasion and metastatic activity. qPCR analysis confirmed increased expression of a whole spectrum of genes associated with mesenchymal characteristics and loss of epithelial specific markers. Additionally, we observed a complete repression of the estrogen receptor 1 (ESR1) expression and downregulation of HER2/NEU. Conclusions. Our data demonstrate for the first time the implication of S6K1 isoforms in the regulation of EMT in MCF-7 cells by triggering for the concomitant onset of a series of possibly parallel events that changes the cell from an epithelial to a mesenchymal type and has a strong negative impact on ESR1 expression. At the tumor level that can mean breast tumor transition to a more aggressive most probably triple negative molecular subtype.
Keywords: S6K1 isoforms, breast cancer, MCF-7 cells, EMT, ESR1
Full text: (PDF, in English)

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