Yıl: 2023 Cilt: 53 Sayı: 3 Sayfa Aralığı: 640 - 646 Metin Dili: İngilizce DOI: 10.55730/1300-0144.5626 İndeks Tarihi: 01-08-2023

Expression of dual-specificity phosphatases in TGFβ1-induced EMT in SKOV3 cells

Öz:
Background/aim: The study aims to profile the dual-specificity phosphatases (DUSP) expression in response to Transforming growth factor β1 (TGFβ1)-induced epithelial- mesenchymal transition (EMT) in ovarian adenocarcinoma cells. Materials and methods: The ovarian adenocarcinoma cell line SKOV3 was used as a TGFβ1-induced EMT model. Cells were incubated with 5 ng/mL TGFβ1 to induce EMT. EMT was confirmed with real-time qPCR, western blot, and immunofluorescence analyses of various EMT markers. Western blot was used to analyze phospho- and total MAPK protein levels. Typical and atypical DUSPs mRNA expression profile was determined by real-time qPCR. Results: The epithelial marker E-cadherin expressions were decreased and mesenchymal EMT markers Snail and Slug expression levels were increased after TGFβ1 induction. Phosphorylation of ERK1/2 and p38 MAPK were enhanced in response to TGFβ1 treatment. The expression of DUSP2, DUSP6, DUSP8, DUSP10, and DUSP13 were decreased while DUSP7, DUSP16, DUSP18, DUSP21, and DUSP27 were increased by TGFβ1. Conclusion: TGFβ1 induced EMT which was accompanied by increased activity of MAPKs, and led to marked changes in expressions of several DUSPs in SKOV3 cells.
Anahtar Kelime: Dual-specificity phosphatases epithelial-mesenchymal transition TGFβ1 ovarian carcinoma SKOV3 MAPK

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık
  • 1. Lheureux S, Gourley C, Vergote I, Oza AM. Epithelial ovarian cancer. The Lancet 2019; 393 (10177): 1240-1253. https://doi. org/10.1016/S0140-6736(18)32552-2
  • 2. Doherty JA, Peres LC, Wang C, Way GP, Greene CS et al. Challenges and opportunities in studying the epidemiology of ovarian cancer subtypes. Current Epidemiology Reports 2017;4: 211-220. https://doi.org/10.1007/s40471-017-0115-y
  • 3. Torre LA, Trabert B, DeSantis CE, Miller KD, Samimi G et al. Ovarian cancer statistics. A Cancer Journal for Clinicians 2018; 68 (4): 284-296. https://doi.org/10.3322/caac.21456
  • 4. Staalduinen JV, Baker D, Dijke PT, Dam HV. Epithelial- mesenchymal-transition-inducing transcription factors: new targets for tackling chemoresistance in cancer? Oncogene 2018;37(48): 6195-6211. https://doi.org/10.1038/s41388-018-0378-x
  • 5. Yang J, Weinberg RA. Epithelial-mesenchymal transition: at the crossroads of development and tumor metastasis. Developmental Cell 2008; 14 (6): 818-829. https://doi. org/10.1016/j.devcel.2008.05.009
  • 6. Moustakas A, Heldin CH. Induction of epithelial-mesenchymal transition by transforming growth factor β. Seminars in Cancer Biology 2012; 22 (5-6): 446-454. https://doi.org/10.1016/j. semcancer.2012.04.002
  • 7. Derynck R, Zhang YE. Smad-dependent and Smad-independent pathways in TGF-beta family signalling. Nature 2003; 425 (6958): 577–584. https://doi.org/10.1038/nature02006
  • 8. Gui T, Sun Y, Shimokado A, Muragaki Y. The roles of mitogen- activated protein kinase pathways in TGF-β-ınduced epithelial- mesenchymal transition. Journal of Signal Transduction 2012; 2012: 289243. https://doi.org/10.1155/2012/289243
  • 9. Lamouille S, Xu J, Derynck R. Molecular mechanisms of epithelial–mesenchymal transition. Nature Reviews Molecular Cell Biology 2014; 15 (3): 178-196. https://doi.org/10.1038/ nrm3758
  • 10. Guzel Tanoglu E, Ozturk S. miR-145 suppresses epithelial- mesenchymal transition by targeting stem cells in Ewing sarcoma cells. Bratislavské Lekárske Listy 2021; 122 (1): 71-77. https://doi.org/10.4149/BLL_2021_009
  • 11. Derynck R, Weinberg RA. EMT and cancer: more than meets the eye. Developmental Cell 2019; 49 (3): 313-316. https://doi. org/10.1016/j.devcel.2019.04.026
  • 12. Hao Y, Baker D, Ten Dijke P. TGF-β-mediated epithelial- mesenchymal transition and cancer metastasis. International Journal of Molecular Sciences 2019; 20 (11): 2767. https://doi. org/10.3390/ijms20112767
  • 13. Jeffrey KL, Camps M, Rommel C, Mackay CR. Targeting dual- specificity phosphatases: manipulating MAP kinase signalling and immune responses. Nature Reviews Drug Discovery 2007; 6 (5): 391-403. https://doi.org/10.1038/nrd2289
  • 14. Seternes OM, Kidger AM, Keyse SM. Dual-specificity MAP kinase phosphatases in health and disease. Biochimica et Biophysica Acta Molecular Cell Research 2019; 1866 (1): 124- 143. https://doi.org/10.1016/j.bbamcr.2018.09.002
  • 15. Liu W, Tian X, Ding X, Zhang L. Expression of Dual- Specificity Phosphatase 2 (DUSP2) in Patients with Serous Ovarian Carcinoma and in SKOV3 and OVCAR3 Cells In Vitro. Medical Science Monitor 2019; 25: 10180-10189. https:// doi.org/10.12659/MSM.919089
  • 16. Sanders BE, Yamamoto TM, McMellen A, Woodruff ER, Berning A et al. Targeting DUSP activity as a treatment for high grade serous ovarian carcinoma. Molecular Cancer Therapeutics 2022; 21(8): 1285-1295. https://doi. org/10.1158/1535-7163.MCT-21-0682
  • 17. Wang J, Zhou JY, Wu GS. ERK-Dependent MKP-1– mediated cisplatin resistance in human ovarian cancer cells. Cancer Research 2007; 67 (24): 11933-11941. https://doi. org/10.1158/0008-5472.CAN-07-5185
  • 18. Bagnato A, Rosano L. Epithelial-mesenchymal transition in ovarian cancer progression: a crucial role for the endothelin axis. Cells Tissues Organs 2007; 185 (1-3): 85-94. https://doi. org/10.1159/000101307
  • 19. Guarino M, Rubino B, Ballabio G. The role of epithelial- mesenchymal transition in cancer pathology. Pathology. 2007; 39 (3): 305-318. https://doi.org/10.1080/00313020701329914
  • 20. MacPhee DJ. Methodological considerations for improving Western blot analysis. Journal of Pharmacological and Toxicological Methods 2010; 61 (2): 171-177. https://doi. org/10.1016/j.vascn.2009.12.001
  • 21. Loret N, Denys H, Tummers P, Berx G. The role of epithelial- to-mesenchymal plasticity in ovarian cancer progression and therapy resistance. Cancers (Basel) 2019; 11 (6): 838. https:// doi.org/10.3390/cancers11060838
  • 22. Lim S, Green JA, Wong H, VanderBurg ME, Crook T. DUSP7 and DUSP8 promoter hypermethylations: Predictors of clinical outcomes in advanced epithelial ovarian carcinoma. Journal of Clinical Oncology 2007; 25 (18): 5501-5501. https://doi. org/10.1200/jco.2007.25.18_suppl.5501
  • 23. Hou YF, Gao SH, Wang P, Zhang HM, Liu LZ et al. 1α,25(OH)₂D₃ suppresses the migration of ovarian cancer skov-3 cells through the ınhibition of epithelial-mesenchymal transition. International Journal of Molecular Sciences 2016; 17 (8): 1285. https://doi.org/10.3390/ijms17081285
  • 24. Fu Y, O’Connor LM, Shepherd TG, Nachtigal MW. The p38 MAPK inhibitor, PD169316, inhibits transforming growth factor β-induced Smad signaling in human ovarian cancer cells. Biochemical and Biophysical Research Communications 2003; 310 (2): 391-397. https://doi.org/10.1016/j.bbrc.2003.09.021
  • 25. James NE, Beffa L, Oliver MT, Borgstadt AD, Emerson JB et al. Inhibition of DUSP6 sensitizes ovarian cancer cells to chemotherapeutic agents via regulation of ERK signaling response genes. Oncotarget 2019; 10 (36): 3315-3327. https:// doi.org/10.18632/oncotarget.26915
  • 26. Guler S, Altunok TH, Sarioglu A, Zik B, Asmaz D et al. Overexpression of dual-specificity phosphatases 4 and 13 attenuates transforming growth factor β1-induced migration and drug resistance in A549 cells in vitro. Biochemical and Biophysical Research Communications 2022; 606: 35-41. https://doi.org/10.1016/j.bbrc.2022.03.090
  • 27. Guler S, Zik B, Yalcin A. Upregulation of dual-specificity phosphatase-26 is required for transforming growth factor β1(TGFβ1)-induced Epithelial-mesenchymal transition in A549 and PANC1 cells. Molecular Biology Reports 2022; 49: 10195-10204. https://doi.org/10.1007/s11033-022-07893-1
  • 28. Wang J, Zhou JY, Kho D, Reiners JJ Jr, Wu GS. Role for DUSP1 (dual-specificity protein phosphatase 1) in the regulation of autophagy. Autophagy 2016; 2:12(10): 1791-1803. https://doi. org/1080/15548627.2016.1203483
  • 29. Sieben NLG, Oosting J, Flanagan AM, Prat J, Roemen GMJM et al. Differential gene expression in ovarian tumors reveals Dusp 4 and Serpina 5 as key regulators for benign behavior of serous borderline tumors. Journal of Clinical Oncology 2005; 23 (29):7257-7264. https://doi.org/10.1200/JCO.2005.02.2541
  • 30. Kwon JY, Seo YR, Ahn WS. Recognition of potential predictive markers for diagnosis in Korean serous ovarian cancer patients at stage IIIc using array comparative genomic hybridization with high resolution. Molecular and Cellular Toxicology 2011; 7: 77-86. https://doi.org/10.1007/s13273-011-0011-3
APA guler s, Yalcin A (2023). Expression of dual-specificity phosphatases in TGFβ1-induced EMT in SKOV3 cells. , 640 - 646. 10.55730/1300-0144.5626
Chicago guler sabire,Yalcin Abdullah Expression of dual-specificity phosphatases in TGFβ1-induced EMT in SKOV3 cells. (2023): 640 - 646. 10.55730/1300-0144.5626
MLA guler sabire,Yalcin Abdullah Expression of dual-specificity phosphatases in TGFβ1-induced EMT in SKOV3 cells. , 2023, ss.640 - 646. 10.55730/1300-0144.5626
AMA guler s,Yalcin A Expression of dual-specificity phosphatases in TGFβ1-induced EMT in SKOV3 cells. . 2023; 640 - 646. 10.55730/1300-0144.5626
Vancouver guler s,Yalcin A Expression of dual-specificity phosphatases in TGFβ1-induced EMT in SKOV3 cells. . 2023; 640 - 646. 10.55730/1300-0144.5626
IEEE guler s,Yalcin A "Expression of dual-specificity phosphatases in TGFβ1-induced EMT in SKOV3 cells." , ss.640 - 646, 2023. 10.55730/1300-0144.5626
ISNAD guler, sabire - Yalcin, Abdullah. "Expression of dual-specificity phosphatases in TGFβ1-induced EMT in SKOV3 cells". (2023), 640-646. https://doi.org/10.55730/1300-0144.5626
APA guler s, Yalcin A (2023). Expression of dual-specificity phosphatases in TGFβ1-induced EMT in SKOV3 cells. Turkish Journal of Medical Sciences, 53(3), 640 - 646. 10.55730/1300-0144.5626
Chicago guler sabire,Yalcin Abdullah Expression of dual-specificity phosphatases in TGFβ1-induced EMT in SKOV3 cells. Turkish Journal of Medical Sciences 53, no.3 (2023): 640 - 646. 10.55730/1300-0144.5626
MLA guler sabire,Yalcin Abdullah Expression of dual-specificity phosphatases in TGFβ1-induced EMT in SKOV3 cells. Turkish Journal of Medical Sciences, vol.53, no.3, 2023, ss.640 - 646. 10.55730/1300-0144.5626
AMA guler s,Yalcin A Expression of dual-specificity phosphatases in TGFβ1-induced EMT in SKOV3 cells. Turkish Journal of Medical Sciences. 2023; 53(3): 640 - 646. 10.55730/1300-0144.5626
Vancouver guler s,Yalcin A Expression of dual-specificity phosphatases in TGFβ1-induced EMT in SKOV3 cells. Turkish Journal of Medical Sciences. 2023; 53(3): 640 - 646. 10.55730/1300-0144.5626
IEEE guler s,Yalcin A "Expression of dual-specificity phosphatases in TGFβ1-induced EMT in SKOV3 cells." Turkish Journal of Medical Sciences, 53, ss.640 - 646, 2023. 10.55730/1300-0144.5626
ISNAD guler, sabire - Yalcin, Abdullah. "Expression of dual-specificity phosphatases in TGFβ1-induced EMT in SKOV3 cells". Turkish Journal of Medical Sciences 53/3 (2023), 640-646. https://doi.org/10.55730/1300-0144.5626