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

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2022-03-23

Authors

Altunok, Tuğba H.
Sarıoğlu, Aybike
Aşmaz, Deniz
Kayapunar, Nuray
Tepedelen, Burcu Erbaykent

Authors

Güler, Sabire
Altunok, Tuğba H.
Sarıoğlu, Aybike
Zik, Berrin
Aşmaz, Deniz
Kayapunar, Nuray
Sönmez, Öner
Tepedelen, Burcu Erbaykent
Yalçın, Abdullah

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Academic Press Inc Elsevier Science

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Abstract

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.

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Epithelial-mesenchymal transition, Transcription, Beta, Emt, Transforming growth factor beta 1, Epithelial-mesenchymal transition, Dual-specificity phosphatase 4, Dual-specificity phosphatase 13, Extracellular signal-regulated kinase, Biochemistry & molecular biology, Biophysics

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