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

Guler, Sabire; Altunok, Tugba Hazal; Sarioglu, Aybike; Zık, Berrin; Asmaz, Deniz; KAYAPUNAR, NURAY VAROL; Sonmez, Oner; Tepedelen, Burcu Erbaykent; Yalçin, Ali

doi:10.1016/j.bbrc.2022.03.090

Cited by 7 publications

(11 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As expected and previously shown, the EMT was successfully induced by TGFβ1 in both A549 [13], and PANC1 cells, as assessed by changes in cell morphology (Fig. 1A).…”

Section: Discussionsupporting

confidence: 89%

“…We had previously reported increases in DUSP1, DUSP7, DUSP15 and DUSP26 mRNAs in A549 cells (Fig. 2A) [13]. Here, we found that, as in A549 cells, TGFβ1 induced DUSP15 and DUSP26 mRNA levels in PANC1 cells (Fig.…”

Section: Tgfβ1 Causes Changes In Expressions Of Duspssupporting

confidence: 81%

“…In the SMAD-independent pathway, one or several of the MAPKs ERK1/2, JNK, and p38 MAPK have been implicated in the EMT process depending on the cellular context and other factors such as the stage of oncogenic transformation [17]. In our recent study [13], we had demonstrated that TGFβ1 signaling only increased the phosphorylation of ERK1/2 in A549 cells. In this study, we observed that the phosphorylation levels of all the MAPK members studied-ERK1/2, JNK, and p38 MAPK-were elevated by TGFβ1 in PANC1 cells, supporting the notion that the effect of TGFβ1 signaling on MAPK activity is context-dependent [18,19].…”

Section: Discussionmentioning

confidence: 93%

“…We recently had shown that TGFβ1 induced an EMT phenotype in the non-small cell lung cancer model A549 cells [13]. To determine if TGFβ1 also induces EMT in the pancreatic adenocarcinoma model PANC1 cells in our hands, we incubated these cells with TGFβ1 (5 mg/ml) for 48 hours, and then the cells were morphologically examined under a microscope.…”

Section: Tgfβ1 Induces Emt and Activates Mapk Pathwaymentioning

confidence: 99%

See 3 more Smart Citations

Upregulation of dual-specificity phosphatase-26 is required for transforming growth factor β1(TGFβ1)-induced Epithelial-mesenchymal transition in A549 and PANC1 cells

2022

Self Cite

View full text Add to dashboard Cite

Background: Transforming Growth Factor β (TGFβ) proteins are potent inducers of the epithelialmesenchymal transition (EMT) in tumor cells. Although mitogen-activated protein kinase (MAPK) family has been shown to be involved in TGFβ-induced EMT, role of Dual Speci city Phosphatases (DUSP), key regulators of MAPK activity, in TGFβ-induced EMT is largely unkonwn.Methods and Results: Real-time qPCR analyses were performed to determine the effect of TGFβ1 on expression of EMT genes and DUSP proteins in the non-small cell lung cancer model A549 and pancreatic adenocarcinoma model PANC1 cells. Western blot analyses were conducted to study the changes in protein levels of EMT proteins and select DUSP proteins, as well as phosphorylations of MAPK proteins upon TGFβ1 stimulation. Small interfering RNA (siRNA) was utilized to reduce expressions of DUSP genes. We observed that the EMT phenotype coincided with increases in phosphorylations of the MAPK proteins ERK1/2, p38MAPK, and JNK upon TGFβ1 stimulation. Real-time qPCR analysis showed increases in DUSP15 and DUSP26 mRNA levels and Western blot analysis con rmed the increase in DUSP26 protein levels in both A549 and PANC1 cells treated with TGFβ1 relative to control. Silencing of DUSP26 expression by siRNA markedly suppressed the effect of TGFβ1 on E-cadherin and mesenchymal genes in the cells.Conclusions: Data provided suggest that TGFβ1 modulates the expression of DUSP genes and that upregulation of DUSP26 may be required for TGFβ1-promoted EMT in A549 and PANC1 cells. Further studies should be carried out to elucidate the requirement of individual DUSPs in TGFβ1-associated EMT in tumor cells.

show abstract

“…As expected and previously shown, the EMT was successfully induced by TGFβ1 in both A549 [13], and PANC1 cells, as assessed by changes in cell morphology (Fig. 1A).…”

Section: Discussionsupporting

confidence: 89%

Section: Tgfβ1 Causes Changes In Expressions Of Duspssupporting

confidence: 81%

Section: Discussionmentioning

confidence: 93%

Section: Tgfβ1 Induces Emt and Activates Mapk Pathwaymentioning

confidence: 99%

See 2 more Smart Citations

Upregulation of dual-specificity phosphatase-26 is required for transforming growth factor β1(TGFβ1)-induced Epithelial-mesenchymal transition in A549 and PANC1 cells

2022

Self Cite

View full text Add to dashboard Cite

show abstract

“…Th DUSP13 gene encodes two isoforms: DUSP13B and DUSP13A 18 . The DUSP4 and DUSP13 co‐expression promotes transforming growth factor beta‐1‐mediated migration, invasion, and chemoresistance in lung cancer 19 …”

Section: Introductionmentioning

confidence: 99%

Systemic analysis identifying PVT1/DUSP13 axis for microvascular invasion in hepatocellular carcinoma

Zhang

et al. 2022

Cancer Medicine

View full text Add to dashboard Cite

show abstract

The p53 tumor suppressor protein activates transcription of DUSP13 isoform from the alternative promoter in intron 3

Krześniak,

Łasut-Szyszka,

Będzińska

et al. 2023

Preprint

View full text Add to dashboard Cite

The p53 tumor suppressor protein is an activator of transcription. Diverse stress factors lead to various sets of posttranslational modifications of p53 what results in different sets of upregulated genes. We noticed that actinomycin D and nutlin-3a (A+N) synergize in inducing activating phosphorylations of p53 and upregulation of selected p53-target genes. Here we found that one of these genes is DUSP13, which codes for poorly-studied, dual-specificity phosphatase having at least two isoforms, one expressed in testis and the other in skeletal muscles. We found that in cancer cells exposed to A+N, DUSP13 is expressed from an alternative promoter in intron 3, what results in expression of isoform named TMDP-L1. The luciferase reporter tests demonstrated that this promoter is activated by both endogenous and ectopically expressed p53. We showed for the first time that mRNA expressed from this promoter actually produces the protein, which can be detected by Western blotting in all examined cancer cell lines with wild-type p53 exposed to A+N. In some cell lines it is also induced by clinically relevant camptothecin. This isoform, fused with green fluorescent protein localizes in perinuclear region of cells. Thus, TMDP-L1 isoform may be an important element of p53-regulated stress response system.

show abstract

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

Cited by 7 publications

References 21 publications

Upregulation of dual-specificity phosphatase-26 is required for transforming growth factor β1(TGFβ1)-induced Epithelial-mesenchymal transition in A549 and PANC1 cells

Upregulation of dual-specificity phosphatase-26 is required for transforming growth factor β1(TGFβ1)-induced Epithelial-mesenchymal transition in A549 and PANC1 cells

Systemic analysis identifying PVT1/DUSP13 axis for microvascular invasion in hepatocellular carcinoma

The p53 tumor suppressor protein activates transcription of DUSP13 isoform from the alternative promoter in intron 3

Contact Info

Product

Resources

About