R-Ras Regulates Migration through an Interaction with Filamin A in Melanoma Cells

Changes in cell adhesion and migration in the tumor microenvironment are key in the initiation and progression of metastasis. R-Ras is one of several small GTPases that regulate cell adhesion and migration on the extracellular matrix, however the mechanism has not been completely elucidated. Using a yeast two-hybrid approach we sought to identify novel R-Ras binding proteins that might mediate its effects on integrins.We identified Filamin A (FLNa) as a candidate interacting protein. FLNa is an actin-binding scaffold protein that also binds to integrin β1, β2 and β7 tails and is associated with diverse cell processes including cell migration. Indeed, M2 melanoma cells require FLNa for motility. We further show that R-Ras and FLNa interact in co-immunoprecipitations and pull-down assays. Deletion of FLNa repeat 3 (FLNaΔ3) abrogated this interaction. In M2 melanoma cells active R-Ras co-localized with FLNa but did not co-localize with FLNa lacking repeat 3. Thus, activated R-Ras binds repeat 3 of FLNa. The functional consequence of this interaction was that active R-Ras and FLNa coordinately increased cell migration. In contrast, co-expression of R-Ras and FLNaΔ3 had a significantly reduced effect on migration. While there was enhancement of integrin activation and fibronectin matrix assembly, cell adhesion was not altered. Finally, siRNA knockdown of endogenous R-Ras impaired FLNa-dependent fibronectin matrix assembly.These data support a model in which R-Ras functionally associates with FLNa and thereby regulates integrin-dependent migration. Thus in melanoma cells R-Ras and FLNa may cooperatively promote metastasis by enhancing cell migration

Identification of Serum MicroRNAs as Novel Non-Invasive Biomarkers for Early Detection of Gastric Cancer

BACKGROUND: To investigate the potential of serum miRNAs as biomarkers for early detection of gastric cancer (GC), a population-based study was conducted in Linqu, a high-risk area of GC in China. METHODOLOGY/PRINCIPAL FINDINGS: All subjects were selected from two large cohort studies. Differential miRNAs were identified in serum pools of GC and control using TaqMan low density array, and validated in individual from 82 pairs of GC and control, and 46 pairs of dysplasia and control by real-time quantitative reverse transcription-polymerase chain reaction. The temporal trends of identified serum miRNA expression were further explored in a retrospective study on 58 GC patients who had at least one pre-GC diagnosis serum sample based on the long-term follow-up population. The miRNA profiling results demonstrated that 16 miRNAs were markedly upregulated in GC patients compared to controls. Further validation identified a panel of three serum miRNAs (miR-221, miR-744, and miR-376c) as potential biomarkers for GC detection, and receiver operating characteristic (ROC) curve-based risk assessment analysis revealed that this panel could distinguish GCs from controls with 82.4% sensitivity and 58.8% specificity. MiR-221 and miR-376c demonstrated significantly positive correlation with poor differentiation of GC, and miR-221 displayed higher level in dysplasia than in control. Furthermore, the retrospective study revealed an increasing trend of these three miRNA levels during GC development (P for trend<0.05), and this panel could classify serum samples collected up to 5 years ahead of clinical GC diagnosis with 79.3% overall accuracy. CONCLUSIONS/SIGNIFICANCE: These data suggest that serum miR-221, miR-376c and miR-744 have strong potential as novel non-invasive biomarkers for early detection of GC

The ecological role of ponds in a changing world

The fifth conference of the European Pond Conservation Network (Luxembourg, June 2012) brought together researchers, environmental managers, and other stakeholders with the aim to share stateof-the-art knowledge on the ecology, management, and conservation of ponds in the context of the many challenges facing the wider water environment. Although well-known ecological patterns apply to most ponds in Europe and elsewhere, recent data highlight that part of the environmental variables governing pond biodiversity remain specific to climatic/ biogeographic regions and to elevation ranges, suggesting that, in addition to common practice, management plans should include range-specific measures. Beyond the contribution of individual ponds to the aquatic and terrestrial life, connected networks of ponds are vital in the provision of new climate space as a response to global climate change, by allowing the observed northward and/or upward movements of species. In terms of services, ponds offer sustainable solutions to key issues of water management and climate change such as nutrient retention, rainfall interception, or carbon sequestration. While the ecological role of ponds is now well established, authoritative research-based advice remains needed to inform future direction in the conservation of small water bodies and to further bridge the gap between science and practice

The ecological role of ponds in a changing world

The fifth conference of the European Pond Conservation Network (Luxembourg, June 2012) brought together researchers, environmental managers, and other stakeholders with the aim to share stateof-the-art knowledge on the ecology, management, and conservation of ponds in the context of the many challenges facing the wider water environment. Although well-known ecological patterns apply to most ponds in Europe and elsewhere, recent data highlight that part of the environmental variables governing pond biodiversity remain specific to climatic/ biogeographic regions and to elevation ranges, suggesting that, in addition to common practice, management plans should include range-specific measures. Beyond the contribution of individual ponds to the aquatic and terrestrial life, connected networks of ponds are vital in the provision of new climate space as a response to global climate change, by allowing the observed northward and/or upward movements of species. In terms of services, ponds offer sustainable solutions to key issues of water management and climate change such as nutrient retention, rainfall interception, or carbon sequestration. While the ecological role of ponds is now well established, authoritative research-based advice remains needed to inform future direction in the conservation of small water bodies and to further bridge the gap between science and practice