title: Vascular endothelial growth factor-C upregulates cortactin and promotes metastasis of esophageal squamous cell carcinoma.
abstract: 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.
authors.affiliation: Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Chih-Ming
authors.initials: CM
authors.lastname: Su
authors.forename: Yen-Hao
authors.initials: YH
authors.lastname: Su
authors.forename: Ching-Feng
authors.initials: CF
authors.lastname: Chiu
authors.forename: Yi-Wen
authors.initials: YW
authors.lastname: Chang
authors.forename: Chih-Chen
authors.initials: CC
authors.lastname: Hong
authors.forename: Yang-Hao
authors.initials: YH
authors.lastname: Yu
authors.forename: Yuan-Soon
authors.initials: YS
authors.lastname: Ho
authors.forename: Chih-Hsiung
authors.initials: CH
authors.lastname: Wu
authors.forename: Chia-Sheng
authors.initials: CS
authors.lastname: Yen
authors.forename: Jen-Liang
authors.initials: JL
authors.lastname: Su
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000737:chemistry* / Q000235:genetics* / Q000556:secondary; D045744:Cell Line, Tumor; D002465:Cell Movement; D058948:Cell Tracking; D051356:Cortactin / Q000032:analysis* / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation; D004938:Esophageal Neoplasms / Q000737:chemistry* / Q000235:genetics* / Q000473:pathology; D055785:Gene Knockdown Techniques; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000556:secondary; D016513:Mice, SCID; D035683:MicroRNAs / Q000378:metabolism; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D014162:Transfection; D015854:Up-Regulation; D042582:Vascular Endothelial Growth Factor C / Q000032:analysis* / Q000378:metabolism
chemical_list: D051356:Cortactin; C545322:MIRN326 microRNA, human; D035683:MicroRNAs; D042582:Vascular Endothelial Growth Factor C; D016392:Proto-Oncogene Proteins pp60(c-src)