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DOI QR Code

Early Growth Response Protein-1 Involves in Transforming Growth factor-β1 Induced Epithelial-Mesenchymal Transition and Inhibits Migration of Non-Small-Cell Lung Cancer Cells

  • Shan, Li-Na (The First Affiliated Hospital of Liaoning Medical University) ;
  • Song, Yong-Gui (Jiangxi University of Traditional Chinese Medicine) ;
  • Su, Dan (Jiangxi University of Traditional Chinese Medicine) ;
  • Liu, Ya-Li (Jiangxi University of Traditional Chinese Medicine) ;
  • Shi, Xian-Bao (The First Affiliated Hospital of Liaoning Medical University) ;
  • Lu, Si-Jing (The First Affiliated Hospital of Liaoning Medical University)
  • Published : 2015.05.18

Abstract

The zinc finger transcription factor EGR 1 has a role in controlling synaptic plasticity, wound repair, female reproductive capacity, inflammation, growth control, apoptosis and tumor progression. Recent studies mainly focused on its role in growth control and apoptosis, however, little is known about its role in epithelial-mesenchymal transition (EMT). Here, we aim to explore whether EGR 1 is involved in TGF-${\beta}1$-induced EMT in non-smallcell lung cancer cells. Transforming growth factor (TGF)-${\beta}1$ was utilized to induce EMT in this study. Western blotting, RT-PCR, and transwell chambers were used to identify phenotype changes. Western blotting was also used to observe changes of the expression of EGR 1. The lentivirus-mediated EGR 1 vector was used to increase EGR 1 expression. We investigated the change of migration to evaluate the effect of EGR 1 on non-small-cell lung cancer cells migration by transwell chambers. After stimulating with TGF-${\beta}1$, almost all A549 cells and Luca 1 cells (Non-small-cell lung cancer primary cells) changed to mesenchymal phenotype and acquired more migration capabilities. These cells also had lower EGR 1 protein expression. Overexpression of EGR 1 gene with EGR 1 vector could decrease tumor cell migration capabilities significantly after adding TGF-${\beta}1$. These data s howed an important role of EGR 1 in the EMT of non-small-cell lung cancer cells, as well as migration.

Keywords

Non-small-cell lung cancer (NSCLC);epithelial-mesenchymal transition (EMT);early growth response

References

  1. Acevedo VD, Gangula RD, Freeman KW, et al (2007). Inducible FGFR-1 activation leads to irreversible prostate adenocarcinoma and an epithelial-to-mesenchymal transition. Cancer cell, 12, 559-71. https://doi.org/10.1016/j.ccr.2007.11.004
  2. BARON V, DUSS S, RHIM J, Mercola D (2003). Antisense to the Early Growth Response-1 Gene (Egr-1) Inhibits Prostate Tumor Development in TRAMP Mice. Ann N Y Acad Sci, 1002, 197-216. https://doi.org/10.1196/annals.1281.024
  3. De Craene B, Berx G (2013). Regulatory networks defining EMT during cancer initiation and progression. Nat Rev Cancer, 13, 97-110. https://doi.org/10.1038/nrc3447
  4. Farrell J, Kelly C, Rauch J, et al (2014). HGF induces epithelialto-mesenchymal transition by modulating the mammalian hippo/MST2 and ISG15 pathways. J Proteome Res, 13, 2874-86. https://doi.org/10.1021/pr5000285
  5. Fu M, Zhang J, Lin Y, et al (2003). Early stimulation and late inhibition of peroxisome proliferator-activated receptor gamma (PPARgamma) gene expression by transforming growth factor beta in human aortic smooth muscle cells: role of early growth-response factor-1 (Egr-1), activator protein 1 (AP1) and Smads. Biochem J, 370, 1019-25. https://doi.org/10.1042/bj20021503
  6. Gorelik L, Flavell RA (2001). Immune-mediated eradication of tumors through the blockade of transforming growth factor-${\beta}$ signaling in T cells. Nat Med, 7, 1118-22. https://doi.org/10.1038/nm1001-1118
  7. Haslehurst AM, Koti M, Dharsee M, et al (2012). EMT transcription factors snail and slug directly contribute to cisplatin resistance in ovarian cancer. BMC cancer, 12, 91. https://doi.org/10.1186/1471-2407-12-91
  8. Huang RP, Fan Y, De Belle I, et al (1997). Decreased Egr-1 expression in human, mouse and rat mammary cells and tissues correlates with tumor formation. Int J Cancer, 72, 102-9. https://doi.org/10.1002/(SICI)1097-0215(19970703)72:1<102::AID-IJC15>3.0.CO;2-L
  9. Li H, Xu L, Li C, et al (2014). Ubiquitin ligase Cbl-b represses IGF-I-induced epithelial mesenchymal transition via ZEB2 and microRNA-200c regulation in gastric cancer cells. Mol Cancer, 13, 136. https://doi.org/10.1186/1476-4598-13-136
  10. Liu YC, Zhou SB, Gao F, et al (2013). Chemotherapy and late course three dimensional conformal radiotherapy for treatment of patients with stage III non- small cell lung cancer. Asian Pac J Cancer Prev, 14, 2663-5. https://doi.org/10.7314/APJCP.2013.14.4.2663
  11. Liu J, Liu YG, Huang R, et al (2007). Concurrent down-regulation of Egr-1 and gelsolin in the majority of human breast cancer cells. Cancer Genomics Proteomics, 4, 377-85.
  12. Liu Y, Zhou YD, Xiao YL, et al (2015). Cyr61/CCN1 Overexpression Induces Epithelial-Mesenchymal Transition Leading to Laryngeal Tumor Invasion and Metastasis and Poor Prognosis. Asian Pac J Cancer Prev, 16, 2659-64. https://doi.org/10.7314/APJCP.2015.16.7.2659
  13. Lo HW, Hsu SC, Xia W, et al (2007). Epidermal growth factor receptor cooperates with signal transducer and activator of transcription 3 to induce epithelial-mesenchymal transition in cancer cells via up-regulation of TWIST gene expression. Cancer Res, 67, 9066-76. https://doi.org/10.1158/0008-5472.CAN-07-0575
  14. Lu YY, Huang XE, Cao J, et al (2013). Phase II study on Javanica oil emulsion injection (Yadanzi$^{(R)}$) combined with chemotherapy in treating patients with advanced lung adenocarcinoma. Asian Pac J Cancer Prev, 14, 4791-4. https://doi.org/10.7314/APJCP.2013.14.8.4791
  15. McLeod C, Thornley A, Veale R, Scott E (1990). The anchorage-dependent and-independent growth of a human SCC cell line: the roles of TGF alpha/EGF and TGF beta. Br J Cancer, 61, 267. https://doi.org/10.1038/bjc.1990.49
  16. Moon Y, Lee M, Yang H (2007). Involvement of early growth response gene 1 in the modulation of microsomal prostaglandin E synthase 1 by epigallocatechin gallate in A549 human pulmonary epithelial cells. Biochem Pharmacol, 73, 125-35. https://doi.org/10.1016/j.bcp.2006.08.017
  17. Padua D, Massague J (2009). Roles of TGF${\beta}$ in metastasis. Cell Res, 19, 89-102. https://doi.org/10.1038/cr.2008.316
  18. Parra E, Gutierrez L, Ferreira J (2013). Increased expression of p21Waf1/Cip1 and JNK with costimulation of prostate cancer cell activation by an siRNA Egr-1 inhibitor. Oncol Rep, 30, 911-6.
  19. Portella G, Cumming SA, Liddell J, et al (1998). Transforming growth factor beta is essential for spindle cell conversion of mouse skin carcinoma in vivo: implications for tumor invasion. Cell Growth Differ, 9, 393-404.
  20. Sanchez-Elsner T, Botella LM, Velasco B, et al (2001). Synergistic cooperation between hypoxia and transforming growth factor-${\beta}$ pathways on human vascular endothelial growth factor gene expression. J Biol Chem, 276, 38527-35. https://doi.org/10.1074/jbc.M104536200
  21. Serrano-Martinez I, McDonald PC, Dedhar S (2012). The integrin-linked kinase (ILK)/Rictor complex is required for TGF {beta}-1-induced epithelial to mesenchymal transition (EMT). Cancer Res, 72, 324. https://doi.org/10.1158/1538-7445.AM2012-324
  22. Shin SY, Kim JH, Baker A, Lim Y, Lee YH (2010). Transcription factor egr-1 is essential for maximal matrix metalloproteinase-9 transcription by tumor necrosis factor${\alpha}$. Mol Cancer Res, 8, 507-19. https://doi.org/10.1158/1541-7786.MCR-09-0454
  23. Sukhatme VP, Cao X, Chang LC, et al (1988). A zinc finger-encoding gene coregulated with c-fos during growth and differentiation, and after cellular depolarization. Cell, 53, 37-43. https://doi.org/10.1016/0092-8674(88)90485-0
  24. Sun S, Ning X, Zhai Y, et al (2014). Egr-1 Mediates Chronic Hypoxia-Induced Renal Interstitial Fibrosis via the PKC/ERK Pathway. Am J Nephrol, 39, 436-48.
  25. Thiel G, Mayer SI, Muller I, Stefano L, Rossler OG (2010). Egr-1-A Ca 2+-regulated transcription factor. Cell calcium, 47, 397-403. https://doi.org/10.1016/j.ceca.2010.02.005
  26. Thiery JP, Acloque H, Huang RY, Nieto MA (2009). Epithelial-mesenchymal transitions in development and disease. Cell, 139, 871-90. https://doi.org/10.1016/j.cell.2009.11.007
  27. Vetter G, Le Bechec A, Muller J, et al (2009). Time-resolved analysis of transcriptional events during SNAI1-triggered epithelial to mesenchymal transition. Biochem Biophys Res Commun, 385, 485-91. https://doi.org/10.1016/j.bbrc.2009.05.025
  28. Virolle T, Krones-Herzig A, Baron V, et al (2003). Egr1 promotes growth and survival of prostate cancer cells identification of novel Egr1 target genes. J Biol Chem, 278, 11802-10. https://doi.org/10.1074/jbc.M210279200
  29. Yu H, Shen Y, Hong J, et al (2015). The contribution of TGF-${\beta}$ in Epithelial-Mesenchymal Transition (EMT): Down-regulation of E-cadherin via snail. Neoplasma, 62, 1-15. https://doi.org/10.4149/neo_2015_002
  30. Yan HA, Shen K, Huang XE (2013). Clinical study on mannan peptide combined with TP regimen in treating patients with non-small cell lung cancer. Asian Pac J Cancer Prev, 14, 4801-4. https://doi.org/10.7314/APJCP.2013.14.8.4801
  31. Zhang H, Chen X, Wang J, et al (2014). EGR1 decreases the malignancy of human non-small cell lung carcinoma by regulating KRT18 expression. Scientific reports, 4.
  32. Zhu QC, Gao RY, Wu W, Qin HL (2013). Epithelial-mesenchymal transition and its role in the pathogenesis of colorectal cancer. Asian Pac J Cancer Prev, 14, 2689-98. https://doi.org/10.7314/APJCP.2013.14.5.2689

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