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- Title
Inhibition of Serum and Glucocorticoid Inducible Kinase 1 (SGK1) in Triple Negative Breast Cancer.
- Authors
HAZNEDAROGLU BENLIOGLU, Elif; DOGAN, Ayse Lale
- Abstract
Glucocorticoid receptor overexpression leads to poor prognosis in breast cancer, particularly in triple-negative phenotype. This poor prognosis has been shown to be due to the activation of SGK1 (serum and glucocorticoid inducible kinase 1). The aim of this study is to assess SGK1 levels and sensitivity of a panel of TNBC (triple-negative breast cancer) cell lines towards SGK1 inhibitor GSK650394 and to assess the effects of inhibition of SGK1 in TNBC cell lines. Among these cell lines, MDA-MB-436 cells, displaying markedly elevated SGK1 and showing high phosphorylation of the SGK1 substrate NDRG1 (N-Myc downstream regulated gene 1), was unresponsive to the SGK1 inhibitor. The other cell lines with varying SGK1 levels (MDA-MB-231, HCC1937 and BT549) showed marked decrease of NDGR1 phosphorylation due to kinase activity inhibition (n= 3, p< 0.05). Intriguingly, despite GSK650394 sensitivity in these cells, pharmacological SGK1 inhibition did not decrease GSK3ß phosphorylation, exhibiting no effect on GSK3ß reactivation (n= 3, p> 0.05). In addition, SGK1 inhibition did not change E-cadherin and vimentin expression showing that epithelial-mesenchymal transition (EMT) phenotype was not suppressed (n= 3, p> 0.05). Accordingly, Slug, Snail and Twist mRNA levels were not affected from SGK1 inhibition (n= 3, p> 0.05). GSK650394 treatment suppressed proliferation in MDA-MB-231 cells and led to a slight decrease in S-phase. The results of this present study supported the hypothesis that SGK1 inhibition strategies could have therapeutic impact in the management of the triple-negative breast cancer.
- Subjects
TRIPLE-negative breast cancer; GLUCOCORTICOID receptors; GLUCOCORTICOIDS; EPITHELIAL-mesenchymal transition; BREAST cancer prognosis
- Publication
UHOD: International Journal of Hematology & Oncology / Uluslararasi Hematoloji Onkoloji Dergisi, 2023, Vol 33, Issue 1, p37
- ISSN
1306-133X
- Publication type
Article
- DOI
10.4999/uhod.236832