Inhibition of Serum and Glucocorticoid Inducible Kinase 1 (SGK1) in Triple Negative Breast Cancer


Haznedaroglu Benlioglu E., DOĞAN A. L.

UHOD - Uluslararasi Hematoloji-Onkoloji Dergisi, vol.33, no.1, pp.37-44, 2023 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 33 Issue: 1
  • Publication Date: 2023
  • Doi Number: 10.4999/uhod.236832
  • Journal Name: UHOD - Uluslararasi Hematoloji-Onkoloji Dergisi
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, EMBASE
  • Page Numbers: pp.37-44
  • Keywords: Triple negative breast neoplasms, Epithelial-mesenchymal transition
  • Hacettepe University Affiliated: Yes

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 unre-sponsive 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 GSK3β phosphorylation, exhibiting no effect on GSK3β 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.