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.

miR-144 inhibits growth and metastasis of cervical cancer cells by targeting VEGFA and VEGFC

“…Anti-VEGF treatment augments the tumor radiation response under normoxic or hypoxic conditions, which is a novel therapeutic strategy in cervical cancer (37). VEGFA and VEGFC, two members of the VEGF family, were recently identified as the predominant tumor metastasis-driving factors in various human cancers types, including renal cell carcinoma (38), hepatocellular carcinoma (39) and cervical cancer (40)(41)(42). The present study identified VEGFA and VEGFC as targets of miR-144 via directly binding to the 3'-UTRs of VEGFA and VEGFC mRNA in a dual luciferase reporter assay.…”

Overexpression of miR-21 promotes the proliferation and migration of cervical cancer cells via the inhibition of PTEN

“…Accumulating evidence has identified molecular mechanisms involved in cervical cancer. Molecules such as vascular endothelial growth factor-C (VEGF-C) (8), Src homology-2 domain containing protein, tyrosine phosphatase-2 (SHP-2) (9), or CD147 isoform-4 (CD147-4) (10) are known to promote the proliferation, migration or invasion of cervical cancers by activating focal adhesion kinases (8), through inhibition of interferon-β production (9), or with an upregulated expression of the cancerous inhibitors PP2A (CIP2A), polo-like kinase (PLK) and cyclin D1 but a downregulated p27 expression (10). By contrast, tumor-suppressive molecules, such as Beclin1 (11) and histone deacetylase (HDAC) 10 (12) have been confirmed to inhibit the invasion and migration of cervical cancer cells by decreasing the expression of VEGF and matrix metalloproteinase (MMP)-9 proteins (11), or through the inhibition of MMP-2 and -9 expression (12).…”

A novel gene signature related to focal adhesions for distinguishing and predicting the prognosis of lung squamous cell carcinoma

“…Filamin-C ( FLNC ) was associated with the risk of glioblastoma multiforme ( 19 ). Vascular endothelial growth factor receptor 3 ( FLT4 ) enhances cervical cancer migration and invasion ( 20 ). Hepatocyte growth factor ( HGF ) increased cisplatin resistance through downregulation of AIF in lung cancer ( 21 ).…”