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Vascular endothelial growth factor receptor-1 mediates migration of human colorectal carcinoma cells by activation of Src family kinases
- Source :
- British Journal of Cancer
- Publication Year :
- 2006
- Publisher :
- Springer Science and Business Media LLC, 2006.
-
Abstract
- Vascular endothelial growth factor (VEGF) is the predominant pro-angiogenic cytokine in human malignancy, and its expression correlates with disease recurrence and poor outcomes in patients with colorectal cancer. Recently, expression of vascular endothelial growth factor receptors (VEGFRs) has been observed on tumours of epithelial origin, including those arising in the colon, but the molecular mechanisms governing potential VEGF-driven biologic functioning in these tumours are not well characterised. In this report, we investigated the role of Src family kinases (SFKs) in VEGF-mediated signalling in human colorectal carcinoma (CRC) cell lines. Vascular endothelial growth factor specifically activated SFKs in HT29 and KM12L4 CRC cell lines. Further, VEGF stimulation resulted in enhanced cellular migration, which was effectively blocked by pharmacologic inhibition of VEGFR-1 or Src kinase. Correspondingly, migration studies using siRNA clones with reduced Src expression confirmed the requirement for Src in VEGF-induced migration in these cells. Furthermore, VEGF treatment enhanced VEGFR-1/SFK complex formation and increased tyrosine phosphorylation of focal adhesion kinase, p130 cas and paxillin. Finally, we demonstrate that VEGF-induced migration is not due, at least in part, to VEGF acting as a mitogen. These results suggest that VEGFR-1 promotes migration of tumour cells through a Src-dependent pathway linked to activation of focal adhesion components that regulate this process.
- Subjects :
- Cancer Research
Immunoblotting
colorectal cancer
Adenocarcinoma
Biology
VEGFR-1
Focal adhesion
chemistry.chemical_compound
Cell Movement
Cell Line, Tumor
Humans
RNA, Small Interfering
Molecular Diagnostics
Paxillin
Vascular Endothelial Growth Factor Receptor-1
Cell migration
VEGF
Enzyme Activation
Gene Expression Regulation, Neoplastic
Vascular endothelial growth factor
Vascular endothelial growth factor B
Vascular endothelial growth factor A
src-Family Kinases
Oncology
chemistry
Mitogen-activated protein kinase
Colonic Neoplasms
Cancer research
biology.protein
Src kinase
Plasmids
Proto-oncogene tyrosine-protein kinase Src
Subjects
Details
- ISSN :
- 15321827 and 00070920
- Volume :
- 94
- Database :
- OpenAIRE
- Journal :
- British Journal of Cancer
- Accession number :
- edsair.doi.dedup.....d541decab2ace64eecbabd086524cf09