Overexpression of dual-specificity phosphatases 4 and 13 attenuates transforming growth factor beta 1-induced migration and drug resistance in A549 cells in vitro

Transforming growth factor-beta (TGF beta) 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 1/2 (ERK1/2) is also involved in promoting and maintaining a mesenchymal phenotype by tumor cells following TGF beta signal activation. As dual-specificity phosphatases (DUSPs) regulate ERK1/2 activity by dephosphorylation, we aimed to examine DUSPs' expression upon TGF beta stimulation and whether DUSPs play a role in the EMT and related phenotypes promoted by TGF beta 1 in A549 cells. We found that TGF beta 1 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 TGF beta 1-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 TGF beta 1-promoted migration, invasion, and chemoresistance in A549 cells. Collectively, this report provides data for the involvement of DUSP4/13 in malignant phenotypes regulated by TGF beta 1 in A549 cells. (C) 2022 Elsevier Inc. All rights reserved.