AI Article Synopsis
- - TGFβ proteins trigger an epithelial-mesenchymal transition (EMT) in carcinoma cells, making them more invasive and resistant to drugs, through pathways involving both SMAD and MAPK proteins.
- - The study focuses on dual-specificity phosphatases (DUSPs) that regulate the activity of ERK1/2, and found that TGFβ1 stimulation decreases the expression of DUSP4 and DUSP13.
- - Co-expressing DUSP4 and DUSP13 in A549 cells dampens TGFβ1-induced ERK1/2 activation and reduces migration, invasion, and drug resistance, highlighting their potential role in combating TGFβ1-driven malignancy.
Article Abstract
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.
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| http://dx.doi.org/10.1016/j.bbrc.2022.03.090 | DOI Listing |
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