Vascular endothelial growth factor C promotes cervical cancer metastasis via up-regulation and activation of RhoA/ROCK-2/moesin cascade
<p>Abstract</p> <p>Background</p> <p>The elevated expression of vascular endothelial growth factor C (VEGF-C) is correlated with clinical cervical cancer metastasis and patient survival, which is interpreted by VEGF-C functions to stimulate angiogenesis and lymphatic ge...
Main Authors: | , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
BMC
2010-04-01
|
Series: | BMC Cancer |
Online Access: | http://www.biomedcentral.com/1471-2407/10/170 |
id |
doaj-778e534b32da40d4b1e1f2c3bd03de26 |
---|---|
record_format |
Article |
spelling |
doaj-778e534b32da40d4b1e1f2c3bd03de262020-11-24T23:17:12ZengBMCBMC Cancer1471-24072010-04-0110117010.1186/1471-2407-10-170Vascular endothelial growth factor C promotes cervical cancer metastasis via up-regulation and activation of RhoA/ROCK-2/moesin cascadeHuang JingheLiu JunxiuLiu QiongshanLi WenCheng YangHe MianFu Xiaodong<p>Abstract</p> <p>Background</p> <p>The elevated expression of vascular endothelial growth factor C (VEGF-C) is correlated with clinical cervical cancer metastasis and patient survival, which is interpreted by VEGF-C functions to stimulate angiogenesis and lymphatic genesis. However, the direct impact of VEGF-C on cervical cancer cell motility remains largely unknown.</p> <p>Methods</p> <p>In this study, we investigated the effects of VEGF-C on actin cytoskeleton remodeling and on cervical cancer cell migration and invasion and how the actin-regulatory protein, moesin regulated these effects through RhoA/ROCK-2 signaling pathway.</p> <p>Results</p> <p>On cervical carcinoma cell line SiHa cells, exposure of VEGF-C triggered remodeling of the actin cytoskeleton and the formation of membrane ruffles, which was required for cell movement. VEGF-C significantly enhanced SiHa cells horizontal migration and three-dimensional invasion into matrices. These actions were dependent on increased expression and phosphorylation of the actin-regulatory protein moesin and specific moesin siRNA severely impaired VEGF-C stimulated-cell migration. The extracellular small GTPase RhoA/ROCK-2 cascade mediated the increased moesin expression and phosphorylation, which was discovered by the use of Y-27632, a specific inhibitor of Rho kinase and by transfected constitutively active, dominant-negative RhoA as well as ROCK-2 SiRNA. Furthermore, in the surgical cervical specimen from the patients with FIGO stage at cervical intra-epithelial neoplasia and I-II cervical squamous cell carcinoma, the expression levels of moesin were found to be significantly correlated with tumor malignancy and metastasis.</p> <p>Conclusions</p> <p>These results implied that VEGF-C promoted cervical cancer metastasis by upregulation and activation of moesin protein through RhoA/ROCK-2 pathway. Our findings offer new insight into the role of VEGF-C on cervical cancer progression and may provide potential targets for cervical cancer therapy.</p> http://www.biomedcentral.com/1471-2407/10/170 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Huang Jinghe Liu Junxiu Liu Qiongshan Li Wen Cheng Yang He Mian Fu Xiaodong |
spellingShingle |
Huang Jinghe Liu Junxiu Liu Qiongshan Li Wen Cheng Yang He Mian Fu Xiaodong Vascular endothelial growth factor C promotes cervical cancer metastasis via up-regulation and activation of RhoA/ROCK-2/moesin cascade BMC Cancer |
author_facet |
Huang Jinghe Liu Junxiu Liu Qiongshan Li Wen Cheng Yang He Mian Fu Xiaodong |
author_sort |
Huang Jinghe |
title |
Vascular endothelial growth factor C promotes cervical cancer metastasis via up-regulation and activation of RhoA/ROCK-2/moesin cascade |
title_short |
Vascular endothelial growth factor C promotes cervical cancer metastasis via up-regulation and activation of RhoA/ROCK-2/moesin cascade |
title_full |
Vascular endothelial growth factor C promotes cervical cancer metastasis via up-regulation and activation of RhoA/ROCK-2/moesin cascade |
title_fullStr |
Vascular endothelial growth factor C promotes cervical cancer metastasis via up-regulation and activation of RhoA/ROCK-2/moesin cascade |
title_full_unstemmed |
Vascular endothelial growth factor C promotes cervical cancer metastasis via up-regulation and activation of RhoA/ROCK-2/moesin cascade |
title_sort |
vascular endothelial growth factor c promotes cervical cancer metastasis via up-regulation and activation of rhoa/rock-2/moesin cascade |
publisher |
BMC |
series |
BMC Cancer |
issn |
1471-2407 |
publishDate |
2010-04-01 |
description |
<p>Abstract</p> <p>Background</p> <p>The elevated expression of vascular endothelial growth factor C (VEGF-C) is correlated with clinical cervical cancer metastasis and patient survival, which is interpreted by VEGF-C functions to stimulate angiogenesis and lymphatic genesis. However, the direct impact of VEGF-C on cervical cancer cell motility remains largely unknown.</p> <p>Methods</p> <p>In this study, we investigated the effects of VEGF-C on actin cytoskeleton remodeling and on cervical cancer cell migration and invasion and how the actin-regulatory protein, moesin regulated these effects through RhoA/ROCK-2 signaling pathway.</p> <p>Results</p> <p>On cervical carcinoma cell line SiHa cells, exposure of VEGF-C triggered remodeling of the actin cytoskeleton and the formation of membrane ruffles, which was required for cell movement. VEGF-C significantly enhanced SiHa cells horizontal migration and three-dimensional invasion into matrices. These actions were dependent on increased expression and phosphorylation of the actin-regulatory protein moesin and specific moesin siRNA severely impaired VEGF-C stimulated-cell migration. The extracellular small GTPase RhoA/ROCK-2 cascade mediated the increased moesin expression and phosphorylation, which was discovered by the use of Y-27632, a specific inhibitor of Rho kinase and by transfected constitutively active, dominant-negative RhoA as well as ROCK-2 SiRNA. Furthermore, in the surgical cervical specimen from the patients with FIGO stage at cervical intra-epithelial neoplasia and I-II cervical squamous cell carcinoma, the expression levels of moesin were found to be significantly correlated with tumor malignancy and metastasis.</p> <p>Conclusions</p> <p>These results implied that VEGF-C promoted cervical cancer metastasis by upregulation and activation of moesin protein through RhoA/ROCK-2 pathway. Our findings offer new insight into the role of VEGF-C on cervical cancer progression and may provide potential targets for cervical cancer therapy.</p> |
url |
http://www.biomedcentral.com/1471-2407/10/170 |
work_keys_str_mv |
AT huangjinghe vascularendothelialgrowthfactorcpromotescervicalcancermetastasisviaupregulationandactivationofrhoarock2moesincascade AT liujunxiu vascularendothelialgrowthfactorcpromotescervicalcancermetastasisviaupregulationandactivationofrhoarock2moesincascade AT liuqiongshan vascularendothelialgrowthfactorcpromotescervicalcancermetastasisviaupregulationandactivationofrhoarock2moesincascade AT liwen vascularendothelialgrowthfactorcpromotescervicalcancermetastasisviaupregulationandactivationofrhoarock2moesincascade AT chengyang vascularendothelialgrowthfactorcpromotescervicalcancermetastasisviaupregulationandactivationofrhoarock2moesincascade AT hemian vascularendothelialgrowthfactorcpromotescervicalcancermetastasisviaupregulationandactivationofrhoarock2moesincascade AT fuxiaodong vascularendothelialgrowthfactorcpromotescervicalcancermetastasisviaupregulationandactivationofrhoarock2moesincascade |
_version_ |
1725584297094545408 |