title: The VEGF-C/Flt-4 axis promotes invasion and metastasis of cancer cells.
abstract: Flt-4, a VEGF receptor, is activated by its specific ligand, VEGF-C. The resultant signaling pathway promotes angiogenesis and/or lymphangiogenesis. This report provides evidence that the VEGF-C/Flt-4 axis enhances cancer cell mobility and invasiveness and contributes to the promotion of cancer cell metastasis. VEGF-C/Flt-4-mediated invasion and metastasis of cancer cells were found to require upregulation of the neural cell adhesion molecule contactin-1 through activation of the Src-p38 MAPK-C/EBP-dependent pathway. Examination of tumor tissues from various types of cancers revealed high levels of Flt-4 and VEGF-C expression that correlated closely with clinical metastasis and patient survival. The VEGF-C/Flt-4 axis, through upregulation of contactin-1, may regulate the invasive capacity in different types of cancer cells.
authors.affiliation: Institute of Toxicology, College of Medicine, National Taiwan University, Taipei 100, Taiwan.
authors.forename: Jen-Liang
authors.initials: JL
authors.lastname: Su
authors.forename: Pan-Chyr
authors.initials: PC
authors.lastname: Yang
authors.forename: Jin-Yuan
authors.initials: JY
authors.lastname: Shih
authors.forename: Ching-Yao
authors.initials: CY
authors.lastname: Yang
authors.forename: Lin-Hung
authors.initials: LH
authors.lastname: Wei
authors.forename: Chang-Yao
authors.initials: CY
authors.lastname: Hsieh
authors.forename: Chia-Hung
authors.initials: CH
authors.lastname: Chou
authors.forename: Yung-Ming
authors.initials: YM
authors.lastname: Jeng
authors.forename: Ming-Yang
authors.initials: MY
authors.lastname: Wang
authors.forename: King-Jen
authors.initials: KJ
authors.lastname: Chang
authors.forename: Mien-Chie
authors.initials: MC
authors.lastname: Hung
authors.forename: Min-Liang
authors.initials: ML
authors.lastname: Kuo
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism; D002465:Cell Movement; D058967:Contactin 1; D058966:Contactins; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D008207:Lymphatic Metastasis / Q000473:pathology; D008297:Male; D051379:Mice; D008875:Middle Aged; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000473:pathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042582:Vascular Endothelial Growth Factor C / Q000378:metabolism*; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000378:metabolism*
chemical_list: C548669:CNTN1 protein, human; D015816:Cell Adhesion Molecules, Neuronal; C548670:Cntn1 protein, mouse; D058967:Contactin 1; D058966:Contactins; D042582:Vascular Endothelial Growth Factor C; D040321:Vascular Endothelial Growth Factor Receptor-3; D020928:Mitogen-Activated Protein Kinases