Possible regulatory role of Snail in NF-κB-mediated changes in E-cadherin in gastric cancer

Hu,Zenan; Liu,Xiaojun; Tang,Zhifeng; Zhou,Yongning; Qiao,Liang

doi:10.3892/or.2012.2200

Possible regulatory role of Snail in NF-κB-mediated changes in E-cadherin in gastric cancer

Authors:
- Zenan Hu
- Xiaojun Liu
- Zhifeng Tang
- Yongning Zhou
- Liang Qiao
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Affiliations: First Clinical Medical School of Lanzhou University, Lanzhou 730000, P.R. China, Department of Gastroenterology and Hepatology, The First Hospital of Lanzhou University, Lanzhou 730000, P.R. China, Storr Liver Unit, Westmead Millennium Institute and Western Clinical School, Department of Medicine, the University of Sydney, Westmead NSW 2145, Australia
Published online on: December 19, 2012 https://doi.org/10.3892/or.2012.2200
Pages: 993-1000

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Abstract

In the present study, we aimed to investigate the involvement of Snail in NF-κB-mediated changes of E-cadherin in gastric cancer. A total of 189 human gastric cancer tissues, and 32 normal gastric mucosal tissues were used to determine the expression levels of NF-κB, E-cadherin and Snail by immunohistochemistry. The correlation between the expression levels and patient clinicopathological data was analyzed. Human gastric cancer cell line SGC7901 was treated with the NF-κB inhibitor PDTC, and the expression levels of E-cadherin and Snail were investigated by qPCR and western blot. NF-κB, E-cadherin and Snail were all detected in normal gastric mucosa and cancer tissues of various differentiation statuses. However, the expression patterns of each protein were different. Strong expression of E-cadherin was detected in normal gastric mucosa, whereas its expression gradually declined in gastric cancer tissues, with weak expression observed in poorly differentiated gastric cancer tissues. In contrast, weak NF-κB and Snail expressions were present in normal gastric mucosa, while their expression levels gradually increased in gastric cancer tissues, with the strongest expression detected in poorly differentiated gastric cancers. The expression of E-cadherin was inversely correlated with that of Snail and NF-κB in the tissues tested. Blockade of NF-κB using its inhibitor PDTC led to a time-dependent reduction in Snail but a time-dependent increase in E-cadherin in SGC7901 cells. These results suggest that in human gastric cancer, loss of E-cadherin may be mediated through NF-κB-induced Snail upregulation. Further studies may reveal whether targeting the NF-κB-Snail-E-cadherin axis could be a useful approach for combating gastric cancer.

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