title: Vascular endothelial growth factor C enhances cervical cancer migration and invasion via activation of focal adhesion kinase.
abstract: Vascular endothelial growth factor C (VEGF-C) is correlated positively with clinical cervical cancer metastasis and survival. Previously we showed that VEGF-C directly activated actin-binding protein moesin, leading to the formation of membrane protrusions. However, whether VEGF-C alters cervical cancer cell adhesion to the extra-cellular matrix is currently unknown. In this study, we investigated the effects of VEGF-C on the formation of focal adhesion complexes, which provide anchoring sites for cell attachment to the extracellular matrix. On cultured cervical carcinoma cell line SiHa cells, VEGF-C enhanced focal adhesion kinase (FAK) phosphorylation. As a result, VEGF-C led to increased formation of focal adhesion complexes and enhanced migration and invasion, which was reversed by siRNA abrogating FAK. VEGF-C resulted in increased interaction of its receptor Flt-4 with non-receptor tyrosine kinase c-Src, leading to c-Src phosphorylation. The specific inhibitor of c-Src kinase, PP2, or the transfection with specific c-Src siRNA largely impaired VEGF-C-enhanced FAK phosphorylation, suggesting that Flt-4/c-Src cascade plays a central role in these processes. These results implied that VEGF-C promotes cervical cancer metastasis by activation of FAK protein through Flt-4/c-Src pathway.
authors: Department of Anesthesiology, Guangzhou First Municipal People's Hospital, Guangzhou, Guangdong Province, China.
authors: Huayun
authors: H
authors: Chen
authors: Kun
authors: K
authors: Suo
authors: Yang
authors: Y
authors: Cheng
authors: Bin
authors: B
authors: Zheng
authors: Lixin
authors: L
authors: Xu
mesh_terms: D000081247:CSK Tyrosine-Protein Kinase; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D051417:Focal Adhesion Kinase 1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009361:Neoplasm Invasiveness / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000556:secondary*; D042582:Vascular Endothelial Growth Factor C / Q000378:metabolism* / Q000494:pharmacology; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000378:metabolism; D019061:src-Family Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D034741:RNA, Small Interfering; D042582:Vascular Endothelial Growth Factor C; D040321:Vascular Endothelial Growth Factor Receptor-3; D000081247:CSK Tyrosine-Protein Kinase; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D019061:src-Family Kinases; C000631346:CSK protein, human