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 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

In-Situ Moisture Assessment in External Walls of Historic Building using Non-Destructive Methods

In-situ measurements of a case study building located in Riga old town near the river Daugava has been carried out in this work. Performed measurements are moisture level of historic masonry, and interstitial monitoring of temperature and relative humidity between the layers of internal insulation and external wall. Obtained results are compared with outdoor weather data. Results show that during the cold months of the year no rising damp problem. No interstitial condensation under the internal insulation, and no risk of mold growth occur. However, the façade of the building tends to be highly influenced by the outdoor weather, and the moisture of the masonry increases during the rain load events

Travel time map of Szczecin main railway station

This article presents the research on time accessibility of public transport. The study concerned the territory of Szczecin and travelling from anywhere in the city to the Main Railway Station. A self-gathering measurement data method was used, which was developed by Authors in earlier studies. Szczecin was selected as the test area because of the shape of the city as well as the location and shape of the excluded areas (areas not accessible to pedestrians or cyclists). Two travel maps were created, for daytime and nighttime public transportation. The study used 162 measurement points arranged in 1x1 km grids. Travel times to the Main Railway Station were calculated with the use of the jakdojade.pl online service. They were calculated for each measurement point and these values were then interpolated with the IDW method. The travel time maps were evaluated by computing the absolute error on the basis of 10 control points. The absolute error was not greater than 4 minutes, what proves very good accuracy of research. The results of the analysis were compared with the population distribution in Szczecin. The interdependence of population distribution and accessibility of the Main Railway Station was analysed

Novel Mechanisms of G Protein-Dependent Regulation of Endothelial Nitric-Oxide Synthase

ABSTRACT Endothelial nitric-oxide synthase (eNOS) plays a crucial role in the regulation of a variety of cardiovascular and pulmonary functions in both normal and pathological conditions. Multiple signaling inputs, including calcium, caveolin-1, phosphorylation by several kinases, and binding to the 90-kDa heat shock protein (Hsp90), regulate eNOS activity. Here, we report a novel mechanism of G protein-dependent regulation of eNOS. We demonstrate that in mammalian cells, the ␣ subunit of heterotrimeric G12 protein (G␣ 12 ) can form a complex with eNOS in an activation-and Hsp90-independent manner. Our data show that G␣ 12 does not affect eNOS-specific activity, but it strongly enhances total eNOS activity by increasing cellular levels of eNOS. Experiments using inhibition of protein or mRNA synthesis show that G␣ 12 increases the expression of eNOS by increasing half-life of both eNOS protein and eNOS mRNA. Small interfering RNA-mediated depletion of endogenous G␣ 12 decreases eNOS levels. A quantitative correlation can be detected between the extent of down-regulation of G␣ 12 and eNOS in endothelial cells after prolonged treatment with thrombin. G protein-dependent increase of eNOS expression represents a novel mechanism by which heterotrimeric G proteins can regulate the activity of downstream signaling molecules