Vascular Endothelial Growth Factor-C Upregulates Cortactin and Promotes Metastasis of Esophageal Squamous Cell Carcinoma

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• 作者：Chih-Ming Su MD (1) (2)
  Yen-Hao Su MD (1) (2) (3)
  Ching-Feng Chiu PhD (3)
  Yi-Wen Chang PhD (3) (4) (5)
  Chih-Chen Hong PhD (3)
  Yang-Hao Yu MD (6) (7)
  Yuan-Soon Ho MD ; PhD (1) (8)
  Chih-Hsiung Wu MD ; PhD (1) (2)
  Chia-Sheng Yen MD (9)
  Jen-Liang Su PhD (10) (11) (12) (3)
  
  1. Graduate Institute of Clinical Medicine ; College of Medicine ; Taipei Medical University ; Taipei ; Taiwan
  2. Department of Surgery ; Division of General Surgery ; Shuang Ho Hospital ; Taipei Medical University ; Taipei ; Taiwan
  3. National Institute of Cancer Research ; National Health Research Institutes ; Zhunan ; Taiwan
  4. The Genomics Research Center ; Academia Sinica ; Taipei ; Taiwan
  5. Graduate Institute of Biochemistry and Molecular Biology ; National Yang-Ming University ; Taipei ; Taiwan
  6. Department of Internal Medicine ; Divisions of Pulmonary and Critical Care Medicine ; China Medical University Hospital ; Taichung ; Taiwan
  7. Graduate Institute of Clinical Medical Science ; China Medical University ; Taichung ; Taiwan
  8. School of Medical Laboratory Science and Biotechnology ; College of Medical Science and Technology ; Taipei Medical University ; Taipei ; Taiwan
  9. Department of General Surgery ; Chi-Mei Medical Center ; Tainan ; Taiwan
  10. Graduate Institute of Cancer Biology ; China Medical University ; Taichung ; Taiwan
  11. Department of Biotechnology ; Asia University ; Taichung ; Taiwan
  12. Center for Molecular Medicine ; China Medical University Hospital ; Taichung ; Taiwan
  
• 刊名：Annals of Surgical Oncology
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：21
• 期：4-supp
• 页码：767-775
• 全文大小：994 KB
• 参考文献：1. WHO. The global burden of disease: 2004 update. 2008;12鈥?.
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• 刊物主题：Surgical Oncology; Oncology; Surgery;
• 出版者：Springer US
• ISSN：1534-4681

文摘

Background Vascular endothelial growth factor-C (VEGF-C) plays an important role during cancer progression and metastasis through activation of VEGF receptors. However, the role of VEGF-C in esophageal squamous cell carcinoma (ESCC) remains unclear. Methods The expression of VEGF-C in advanced stages of esophageal cancer was examined by immunohistochemistry and its expression was correlated with the protein level of cortactin (CTTN) by Western blot. Knockdown and overexpression of the CTTN protein were respectively performed to investigate the effects on VEGF-C-enhanced ESCC migration/invasion by in vitro transwell assay, cell tracing assay, and tumor growth/experimental metastasis in animal models. Results The expression of VEGF-C was positively correlated with tumor status and poor clinical prognosis in patient with esophageal cancer. VEGF-C-upregulated CTTN expression contributed the migration/invasive abilities of ESCC cell lines through Src-mediated downregulation of miR-326. Moreover, knockdown of CTTN expression significantly abolished VEGF-C-induced tumor growth and experimental lung metastasis in vivo. Conclusions Upregulation of CTTN is critical for VEGF-C-mediated tumor growth and metastasis of ESCC. These finding suggest that VEGF-C upregulated CTTN expression through Src-mediated downregulation of miR-326. CTTN may be a crucial mediator of VEGF-C-involved ESCC metastasis, which provides a potential target for diagnosis and individualized treatment in clinical practice.