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Nuclear expression of Twist promotes lymphatic metastasis in esophageal squamous cell carcinoma.

Abstract
Twist-1 protein (also called Twist) has been suggested to be involved in tumor epithelial-mesenchymal transition (EMT) related progression, however, the mechanism by which twist promotes lymph node metastasis is not fully understood. In the present study, we found that nuclear twist expression is clearly correlated with lymph node (LN) metastasis as determined by immunohistochemistry (IHC). A highly invasive EC109 cell subline, EC109-P, was established by repeated in vitro transwell isolations for the cell model. Immunofluorescence (IF) assay demonstrated that nuclear twist expression was markedly higher in the highly invasive EC109-P cell line when compared with EC109 and EC9706 cells. Based on our cell model, the function and mechanism by which twist regulates LN metastasis in ESCC was investigated. The results showed that the overexpression of Twist could significantly increase the invasion and VEGF-C expression of EC9706 cells, whereas the knockdown of twist expression results in the opposite effects. This finding was further strengthened by the results of the analysis of co-expression of twist and VEGF-C by IHC in ESCC clinical samples. In summary, our study indicates that nuclear twist plays an important role in ESCC lymphatic metastasis by increasing the expression of VEGF-C. The combination of twist and VEGF-C detection could be a reliable prediction of LN metastasis in ESCC.
AuthorsTaiqian Gong, Zengfu Xue, Shanhong Tang, Xiushan Zheng, Guanghui Xu, Liucun Gao, Guohong Zhao, Liu Hong, Guangbo Tang, Hongwei Zhang, Ruwen Wang, Yaoguang Jiang, Daiming Fan
JournalCancer biology & therapy (Cancer Biol Ther) Vol. 13 Issue 8 Pg. 606-13 (Jun 2012) ISSN: 1555-8576 [Electronic] United States
PMID22441818 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Twist-Related Protein 1
  • Vascular Endothelial Growth Factor C
Topics
  • Adult
  • Aged
  • Carcinoma, Squamous Cell (genetics, metabolism, pathology)
  • Cell Nucleus (genetics, metabolism)
  • Esophageal Neoplasms (genetics, metabolism, pathology)
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lymph Nodes (metabolism, pathology)
  • Male
  • Middle Aged
  • Neoplasm Invasiveness (genetics)
  • Neoplasm Metastasis (genetics)
  • Twist-Related Protein 1 (genetics, metabolism)
  • Vascular Endothelial Growth Factor C (genetics, metabolism)

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