COX-2 regulates E-cadherin expression through the NF-κB/Snail signaling pathway in gastric cancer Corrigendum in /10.3892/ijmm.2022.5083

Chen,Zhaofeng; Liu,Min; Liu,Xiaojun; Huang,Shanshan; Li,Linlin; Song,Bo; Li,Hailong; Ren,Qian; Hu,Zenan; Zhou,Yongning; Qiao,Liang

doi:10.3892/ijmm.2013.1376

COX-2 regulates E-cadherin expression through the NF-κB/Snail signaling pathway in gastric cancer

Corrigendum in: /10.3892/ijmm.2022.5083

Authors:
- Zhaofeng Chen
- Min Liu
- Xiaojun Liu
- Shanshan Huang
- Linlin Li
- Bo Song
- Hailong Li
- Qian Ren
- Zenan Hu
- Yongning Zhou
- Liang Qiao
View Affiliations

Affiliations: Division of Gastroenterology and Hepatology, The First Hospital of Lanzhou University, Lanzhou, Gansu, P.R. China, Division of Gastroenterology and Hepatology, Dongying District Hospital, Dongying, Shandong, P.R. China, Storr Liver Unit, Westmead Millennium Institute, Western Clinical School, Faculty of Medicine, Westmead Hospital, University of Sydney, Westmead, NSW, Australia
Published online on: May 10, 2013 https://doi.org/10.3892/ijmm.2013.1376
Pages: 93-100

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Cyclooxygenase-2 (COX-2) participates in cancer invasion and metastasis by decreasing the expression of E-cadherin. However, the molecular mechanisms through which COX-2 regulates E-cadherin expression and function have not yet been fully elucidated. The aim of this study was to investigate the possible molecular mechanisms through which COX-2 regulates E-cadherin expression in gastric cancer. The mRNA and protein expression of COX-2, nuclear factor-κB (NF-κB), Snail and E-cadherin was detected in gastric cancer cells by quantitative PCR and western blot analysis, respectively. The expression of these genes was also detected in healthy gastric mucosa and gastric cancer tissues by immunohistochemistry. We detected various levels of COX-2, nuclear factor-κB (NF-κB), Snail and E-cadherin expression in the normal gastric mucosa and cancer tissues; however, the expression patterns differed: the increased expression of COX-2, NF-κB and Snail was observed in the gastric cancer tissues, whereas there was a considerable reduction in E-cadherin expression in the cancer tissues compared to the normal gastric mucosa. The expression patterns of COX-2, NF-κB and Snail were similar. The increased expression of COX-2 in the gastric cancer tissues closely correlated with the increased expression of NF-κB and Snail, but inversely correlated with the expression of E-cadherin. Treatment of the SGC7901 cells (which express high levels of COX-2) with celecoxib, a COX-2 inhibitor, not only led to a marked dose- and time-dependent decrease in the expression of COX-2, NF-κB and Snail, but also led to a significant increase in the expression of E-cadherin, and this was associated with a reduction in cell invasion. By contrast, the same treatment did not alter the expression of these genes in another gastric cancer cell line, MGC803 (which barely expresses COX-2). These data suggest that COX-2 regulates the expression of E-cadherin through the NF-κB and Snail signaling pathway in gastric cancer.

View Figures

View References

1.	The GLOBOCAN project. http://globocan.iarc.fr/. 2008
2.	Gumbiner BM: Regulation of cadherin-mediated adhesion in morphogenesis. Nat Rev Mol Cell Biol. 6:622–634. 2005. View Article : Google Scholar : PubMed/NCBI
3.	Doukoumetzidis K and Hengartner MO: Cell biology: dying to hold you. Nature. 451:530–531. 2008. View Article : Google Scholar : PubMed/NCBI
4.	Winter JM, Ting AH, Vilardell F, et al: Absence of E-cadherin expression distinguishes noncohesive from cohesive pancreatic cancer. Clin Cancer Res. 14:412– 418. 2008. View Article : Google Scholar : PubMed/NCBI
5.	Müller-Decker K and Fürstenberger G: The cyclooxygenase-2-mediated prostaglandin signaling is causally related to epithelial carcinogenesis. Mol Carcinog. 46:705–710. 2007.PubMed/NCBI
6.	Muraki C, Ohga N, Hida Y, et al: Cyclooxygenase-2 inhibition causes antiangiogenic effects on tumor endothelial and vascular progenitor cells. Int J Cancer. 130:59–70. 2012. View Article : Google Scholar : PubMed/NCBI
7.	Zhou Y, Ran J, Tang C, et al: Effect of celecoxib on E-cadherin, VEGF, microvessel density and apoptosis in gastric cancer. Cancer Biol Ther. 6:269–275. 2007. View Article : Google Scholar : PubMed/NCBI
8.	Rao DS, Gui D, Koski ME, et al: An inverse relation between COX-2 and E-cadherin expression correlates with aggressive histologic features in prostate cancer. Appl Immunohistochem Mol Morphol. 14:375–383. 2006. View Article : Google Scholar : PubMed/NCBI
9.	Erdem H, Gündogdu C and Sipal S: Correlation of E-cadherin, VEGF, COX-2 expression to prognostic parameters in papillary thyroid carcinoma. Exp Mol Pathol. 90:312–317. 2011. View Article : Google Scholar : PubMed/NCBI
10.	Hu Z, Liu X, Tang Z, et al: Possible regulatory role of Snail in NF-κB-mediated changes in E-cadherin in gastric cancer. Oncol Rep. 29:993–1000. 2013.PubMed/NCBI
11.	Thiel A, Mrena J and Ristimäki A: Cyclooxygenase-2 and gastric cancer. Cancer Metastasis Rev. 30:387–395. 2011. View Article : Google Scholar
12.	Li Y, Tan BB, Fan LQ, et al: Expression of COX-2, survivin in regional lymph node metastases of gastric carcinoma and the correlation with prognosis. Hepatogastroenterology. 57:1435–1441. 2010.PubMed/NCBI
13.	Cho SJ, Kim N, Kim JS, et al: The anti-cancer effect of COX-2 inhibitors on gastric cancer cells. Dig Dis Sci. 52:1713–1121. 2007. View Article : Google Scholar : PubMed/NCBI
14.	Yashiro M, Nakazawa K, Tendo M, et al: Selective cyclooxygenase-2 inhibitor downregulates the paracrine epithelial-mesenchymal interactions of growth in scirrhous gastric carcinoma. Int J Cancer. 120:686–693. 2007. View Article : Google Scholar
15.	Jiménez P, García A, Santander S and Piazuelo E: Prevention of cancer in the upper gastrointestinal tract with COX-inhibition. Still an option? Curr Pharm Des. 13:2261–2273. 2007.PubMed/NCBI
16.	Winter JM, Ting AH, Vilardell F, et al: Absence of E-cadherin expression distinguishes noncohesive from cohesive pancreatic cancer. Clin Cancer Res. 14:412–418. 2008. View Article : Google Scholar : PubMed/NCBI
17.	Spaderna S, Schmalhofer O, Wahlbuhl M, et al: The transcriptional repressor ZEB1 promotes metastasis and loss of cell polarity in cancer. Cancer Res. 68:537–544. 2008. View Article : Google Scholar : PubMed/NCBI
18.	Neal CL, Henderson V, Smith BN, et al: Snail transcription factor negatively regulates maspin tumor suppressor in human prostate cancer cells. BMC Cancer. 12:3362012. View Article : Google Scholar : PubMed/NCBI
19.	Dhasarathy A, Phadke D, Mav D, et al: The transcription factors Snail and Slug activate the transforming growth factor-beta signaling pathway in breast cancer. PLoS One. 6:e265142011. View Article : Google Scholar : PubMed/NCBI
20.	Becker KF, Rosivatz E, Blechschmidt K, et al: Analysis of the E-cadherin repressor Snail in primary human cancers. Cells Tissues Organs. 185:204–212. 2007. View Article : Google Scholar : PubMed/NCBI
21.	Blechschmidt K, Kremmer E, Hollweck R, et al: The E-cadherin repressor snail plays a role in tumor progression of endometrioid adenocarcinomas. Diagn Mol Pathol. 16:222–228. 2007. View Article : Google Scholar : PubMed/NCBI
22.	Mazda M, Nishi K, Naito Y and Ui-Tei K: E-cadherin E-cadherin is transcriptionally activated via suppression of ZEB1 transcriptional repressor by small RNA-mediated gene silencing. PLoS One. 6:e286882011. View Article : Google Scholar : PubMed/NCBI
23.	Francí C, Gallén M, Alameda F, et al: Snail1 protein in the stroma as a new putative prognosis marker for colon tumours. PLoS One. 4:e55952009.PubMed/NCBI
24.	Dohadwala M, Yang SC, Luo J, et al: Cyclooxygenase-2-dependent regulation of E-cadherin: prostaglandin E(2) induces transcriptional repressors ZEB1 and snail in non-small cell lung cancer. Cancer Res. 66:5338–5345. 2006. View Article : Google Scholar : PubMed/NCBI
25.	Wu Y, Deng J, Rychahou PG, et al: Stabilization of snail by NF-kappaB is required for inflammation-induced cell migration and invasion. Cancer Cell. 15:416–428. 2009. View Article : Google Scholar : PubMed/NCBI
26.	Stanisavljevic J, Porta-de-la-Riva M, Batlle R, et al: The p65 subunit of NF-κB and PARP1 assist Snail1 in activating fibronectin transcription. J Cell Sci. 124:4161–4171. 2011.
27.	Madrid LV, Mayo MW, Reuther JY and Baldwin AS Jr: Akt stimulates the transactivation potential of the RelA/p65 subunit of NF-kappaB through utilization of the IkappaB kinase and activation of the mitogen-activated protein kinase p38. J Biol Chem. 276:18934–18940. 2011. View Article : Google Scholar : PubMed/NCBI
28.	Leng J, Han C, Demetris AJ, et al: Cyclooxygenase-2 promotes hepatocellular carcinoma cell growth through Akt activation: evidence for Akt inhibition in celecoxib-induced apoptosis. Hepatology. 38:756–768. 2003. View Article : Google Scholar : PubMed/NCBI