ZEB2 Promotes the Metastasis of Gastric Cancer and Modulates Epithelial Mesenchymal Transition of Gastric Cancer Cells
- 511 Downloads
Invasion and metastasis are the hallmarks of advanced gastric cancer progression. Therefore, it is urgent to overcome metastasis in order to improve the survival of gastric cancer patients.
This study aimed to examine the expression of ZEB2 in gastric cancer samples and analyze its correlation with clinicopathologic features. In addition, the molecular mechanism by which ZEB2 contributes to gastric cancer metastasis will be explored.
ZEB2 expression in clinical gastric cancer samples was evaluated by immunohistochemical analysis. ZEB2 was knocked-down in HGC27 gastric cancer cells by shRNA and the effects on cell invasion and migration were examined by in vitro cell invasion and migration assays. The expression of epithelial marker E-cadherin, mesenchymal markers fibronecin and vimentin, and MMPs was detected by western blot analysis.
The expression of ZEB2 was positively correlated with the depth of invasion, lymph node metastasis and TNM stage. In addition, patients with positive ZEB2 expression showed a significantly shorter overall survival time than did patients with negative ZEB2. shRNA mediated knockdown of ZEB2 resulted in reduced invasion and migration of HGC27 cells, along with the upregulation of E-cadherin and downregulation of fibronecin, vimentin, MMP2, and MMP9.
ZEB2 expression is closely associated with the clinicopathological parameters of gastric cancer. ZEB2 promotes gastric cancer cell migration and invasion at least partly via the regulation of epithelial-mesenchymal transition. ZEB2 is a potential target for gene therapy of aggressive gastric cancer.
KeywordsZEB2 Gastric cancer Migration Invasion Epithelial-mesenchymal transition
The research was supported by the Project of Science and Technology Bureau of Hunan Province, China (2011FJ6025).
Conflict of interest
- 13.Van de Putte T, Maruhashi M, Francis A, et al. Mice lacking Zfhx1b, the gene that codes for Smad-interacting protein-1, reveal a role for multiple neural crest cell defects in the etiology of Hirschsprung disease-mental retardation syndrome. Am J Hum Genet. 2003;72:465–470.PubMedCrossRefGoogle Scholar
- 22.Sobin LH, Gospodarowicz MK, Wittekind C. UICC TNM classification of malignant tumours. 7th ed. New York: Wiley-Blackwell; 2009.Google Scholar