Overexpression of dual-specificity phosphatases 4 and 13 attenuates transforming growth factor β1-induced migration and drug resistance in A549 cells in vitro


GÜLER S. , Altunok T. H. , Sarioglu A., ZIK B. , Asmaz D., Kayapunar N., ...More

Biochemical and Biophysical Research Communications, vol.606, pp.35-41, 2022 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 606
  • Publication Date: 2022
  • Doi Number: 10.1016/j.bbrc.2022.03.090
  • Title of Journal : Biochemical and Biophysical Research Communications
  • Page Numbers: pp.35-41
  • Keywords: Transforming growth factor beta 1, Epithelial-mesenchymal transition, Dual-specificity phosphatase 4, Dual-specificity phosphatase 13, Extracellular signal-regulated kinase, EPITHELIAL-MESENCHYMAL TRANSITION, TRANSCRIPTION, BETA, EMT

Abstract

© 2022 Elsevier Inc.Transforming growth factor-beta (TGFβ) proteins induce an epithelial-mesenchymal transition (EMT) programme that is associated with increased invasive and drug-resistant phenotype of carcinoma cells. In addition to the canonical pathway involving SMAD proteins, the mitogen-activated kinase (MAPK) pathway via extracellular signal-regulated kinases ½ (ERK1/2) is also involved in promoting and maintaining a mesenchymal phenotype by tumor cells following TGFβ signal activation. As dual-specificity phosphatases (DUSPs) regulate ERK1/2 activity by dephosphorylation, we aimed to examine DUSPs’ expression upon TGFβ stimulation and whether DUSPs play a role in the EMT and related phenotypes promoted by TGFβ1 in A549 cells. We found that TGFβ1 stimulation led to marked changes in several DUSP proteins, including significant decreases in DUSP4 and DUSP13 expressions. We then showed that the ectopic co-expression of DUSP4/13 suppresses TGFβ1-induced ERK1/2 phosphorylation and protein levels of the EMT transcription factors Snail and Slug proteins. We then demonstrated that DUSP4/13 co-expression partially inhibited TGFβ1-promoted migration, invasion, and chemoresistance in A549 cells. Collectively, this report provides data for the involvement of DUSP4/13 in malignant phenotypes regulated by TGFβ1 in A549 cells.