title: 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.
authors.affiliation: State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, China.
authors.forename: Taiqian
authors.initials: T
authors.lastname: Gong
authors.forename: Zengfu
authors.initials: Z
authors.lastname: Xue
authors.forename: Shanhong
authors.initials: S
authors.lastname: Tang
authors.forename: Xiushan
authors.initials: X
authors.lastname: Zheng
authors.forename: Guanghui
authors.initials: G
authors.lastname: Xu
authors.forename: Liucun
authors.initials: L
authors.lastname: Gao
authors.forename: Guohong
authors.initials: G
authors.lastname: Zhao
authors.forename: Liu
authors.initials: L
authors.lastname: Hong
authors.forename: Guangbo
authors.initials: G
authors.lastname: Tang
authors.forename: Hongwei
authors.initials: H
authors.lastname: Zhang
authors.forename: Ruwen
authors.initials: R
authors.lastname: Wang
authors.forename: Yaoguang
authors.initials: Y
authors.lastname: Jiang
authors.forename: Daiming
authors.initials: D
authors.lastname: Fan
mesh_terms: D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics; D009362:Neoplasm Metastasis / Q000235:genetics; D051879:Twist-Related Protein 1 / Q000235:genetics / Q000378:metabolism*; D042582:Vascular Endothelial Growth Factor C / Q000235:genetics / Q000378:metabolism
chemical_list: D051879:Twist-Related Protein 1; D042582:Vascular Endothelial Growth Factor C