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SÖNMEZ, ÖNER

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    Overexpression of dual-specificity phosphatases 4 and 13 attenuates transforming growth factor β1-induced migration and drug resistance in A549 cells in vitro
    (Academic Press Inc Elsevier Science, 2022-03-23) Güler, Sabire; Altunok, Tuğba H.; Sarıoğlu, Aybike; Zik, Berrin; Aşmaz, Deniz; Kayapunar, Nuray; Sönmez, Öner; Tepedelen, Burcu Erbaykent; Yalçın, Abdullah; GÜLER, SABİRE; Altunok, Tuğba H.; Sarıoğlu, Aybike; ZIK, BERRİN; Aşmaz, Deniz; Kayapunar, Nuray; SÖNMEZ, ÖNER; Tepedelen, Burcu Erbaykent; YALÇIN, ABDULLAH; Bursa Uludağ Üniversitesi/Veteriner Fakültesi/Histoloji ve Embriyoloji Anabilim Dalı.; Bursa Uludağ Üniversitesi/Veteriner Fakültesi/Biyokimya Anabilim Dalı.; Bursa Uludağ Üniversitesi/Fen-Edebiyat Fakültesi/Moleküler Biyoloji ve Genetik Anabilim Dalı.; 0000-0002-7367-6859; 0000-0003-1263-3799; 0000-0002-1062-332X; 0000-0001-8519-8375; 0000-0002-8287-6617; 0000-0001-6468-8535; AAH-8807-2021; KMY-2643-2024; S-2474-2018; AAH-9810-2021; HPG-0648-2023; GXM-5514-2022; DTN-7054-2022; AAH-6436-2021; ABI-4164-2020
    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.