Snail | EPFL Graph Search

A snail is a shelled gastropod. The name is most often applied to land snails, terrestrial pulmonate gastropod molluscs. However, the common name snail is also used for most of the members of the molluscan class Gastropoda that have a coiled shell that is large enough for the animal to retract completely into. When the word "snail" is used in this most general sense, it includes not just land snails but also numerous species of sea snails and freshwater snails. Gastropods that naturally lack a shell, or have only an internal shell, are mostly called slugs, and land snails that have only a very small shell (that they cannot retract into) are often called semi-slugs. Snails have considerable human relevance, including as food items, as pests, and as vectors of disease, and their shells are used as decorative objects and are incorporated into jewelry. The snail has also had some cultural significance, tending to be associated with lethargy. The snail has also been used as a figure of s

The role of Snail in non-small cell lung cancer

Svenja Johanna Groeneveld

The epithelial-to-mesenchymal transition (EMT) is a developmental program frequently reactivated in cancer. It plays an important role in several aspects of tumor progression, particularly in the acquisition of invasive capacities facilitating metastasis. Beyond invasion, EMT endows cancer cells with additional characteristics essential for metastatic dissemination and has been extensively studied in breast and colorectal cancer. Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths worldwide and the majority of NSCLC patients is diagnosed with metastatic disease. The expression of the key EMT transcription factor Snail is correlated with a poor prognosis in NSCLC patients, while it is unclear whether Snail contributes to disease progression by actually facilitating metastasis formation. During EMT, the metabolism of a cancer cell changes, likely to meet the environmental challenges faced during the metastatic process. In this line, we have previously reported (Masin et al, 2014) that the glucose transporter GLUT3 is upregulated during EMT in human NSCLC cell lines. Here, we demonstrate that the rate-limiting enzyme of the hexosamine biosynthesis pathway (HBP) correlates with GLUT3 in NSCLC. This pathway produces a substrate for O-linked protein GlcNAcylations important during EMT, as they â for example â stabilize the Snail protein. Glutamine-fructose-6-phosphate amidotransferase 2 (GFPT2) was specifically upregulated during EMT, while its isoenzyme GFPT1 was unaffected. Furthermore, our results points towards a putative regulation of GLUT3 expression by GFPT2, possibly involving STAT3 signaling. We thus provide evidence for a possible reactivation of a developmental metabolic program during EMT in NSCLC. Chronic inflammation is an important disease-promoting factor during lung tumorigenesis, emphasizing the role of the immune system in this cancer type. Overexpressing or silencing Snail in the immunocompetent autochthonous KrasLSL-G12D/+;p53fl/fl mouse model of lung adenocarcinoma uncovered a substantial influence of Snail on the tumor microenvironment. An extensive analysis of tumor histology, gene and protein expression and immune infiltration revealed that while Snail did not contribute to metastasis formation, it accelerated growth and malignant progression of the lung tumors, reducing the survival time of the mice. Snail decreased B lymphocyte, while enhancing neutrophil infiltration of the tumors. Intriguingly, through the secretion of a soluble factor, Snail induced a feed-forward loop of neutrophil recruitment via Cxcl2, produced by neutrophils themselves. In our recently published collaborative work (Faget, Groeneveld et al, 2017), we identified neutrophils as main contributors to disease progression. We furthermore provided evidence for a vicious cycle formed between Snail expressing cancer cells and neutrophils in lung tumors, as neutrophils were found to impair angiogenesis, resulting in hypoxia and enhanced Snail expression. In addition, we found that Snail repressed the Dlk1-Dio3 locus, containing the genomeâs largest miRNA cluster and recently implicated in NSCLC, in tumor-infiltrating immune cells via a paracrine mechanism.

EPFL2018

Silver nanoparticle effects on simple stream food webs and ecosystem processes

Carmen Omayra Gil Allué

With the global nanotechnology market growing rapidly, nanomaterials are being increasingly released into aquatic environments, where they can undergo modifications and sedimentation, which will put benthic organisms at risk. Of particular interest is the study of nanomaterial effects on periphyton, a community of auto- and heterotrophic microorganisms embedded in an extracellular polymer matrix that covers submerged surfaces in aquatic ecosystems. Although periphyton assumes important functions in ecosystems, like primary production, little information is available on its sensitivity to nanomaterials and how these might be transferred to higher trophic levels in food webs. In the present thesis, effects of short- and long-term exposures to citrate-coated silver nanoparticles (AgNP, 35 nm) and silver ions (Ag+, dosed as AgNO3) were assessed on periphyton in microcosm studies for periods between 2 hours and 21 days. After exposure, primary production, secondary production, photosynthetic yield, microbial respiration and potential extracellular enzyme activity were measured. Moreover, addition of an aquatic snail, Physa acuta, feeding on periphyton allowed the assessment of effects of AgNP on an aquatic herbivore and trophic transfer efficiency. Contaminated (AgNP and AgNO3) and uncontaminated periphyton was offered to snails in a 5-day experiment to determine silver uptake and the mortality, feeding rate and reproduction of the snails. Our findings show that all endpoints measured in periphyton were affected by both AgNP and AgNO3 during short-term exposure, but AgNO3 was more toxic on a total silver mass basis than AgNP. Concentrations causing a 50% reduction in the different endpoints (EC50) ranged from 17 to 83 µM AgNP and from 2 to 4 µM AgNO3. Exposure of periphyton in the presence of silver ion ligands to complex Ag+ (ca. 1% of total silver in AgNP suspensions) prevented AgNP toxicity to most endpoints, confirming that the observed toxic effects were caused by the bioavailable Ag+. An exception was the extracellular enzyme leucine aminopeptidase, which was directly affected by AgNP. Concentrations of AgNP and AgNO3 that caused low toxicity during short-term exposure also caused effects on periphyton functions upon long-term exposure, with algae and bacteria being differently affected. Periphyton exposed to 10 µM AgNP for 21 days showed a 63% decrease in primary production and a 246% increase in bacterial secondary production per unit of total periphyton biomass. The community composition exposed to AgNP or AgNO3 differed from that of the control and also from each other. Furthermore, AgNP-exposed communities were more tolerant to subsequent AgNP exposure. Trophic transfer of silver from contaminated periphyton to snails occurred efficiently, independently of the silver form. Feeding rate of snails on AgNO3-exposed communities was 50% lower than on controls, and disturbance of digestion was evident upon feeding on both AgNP- and AgNO3-exposed communities. No changes in the mortality or egg production of the snails were observed. However, the hatching success of eggs from snails that fed on contaminated periphyton was reduced by more than 79%, and 28-day old embryos showed malformations. Overall, this study clearly identified damaging effects of AgNP on periphyton, with consequent indirect impacts on a consumer, trophic relationships and stream ecosystem processes.

EPFL2015

Snail mediates repression of the Dlk1-Dio3 locus in lung tumor-infiltrating immune cells

Julien Robert Rémi Faget, Svenja Johanna Groeneveld, Etienne Meylan, Nadine Zangger

The epithelial-mesenchymal transition-inducing transcription factor Snail contributes to tumor progression in different malignancies. In the present study, we used a transcriptomics approach to elucidate the mechanism of Snail-mediated tumor growth promotion in a KrasLSL-G12D/+;p53fl/fl mouse model of lung adenocarcinoma. We discovered that Snail mediated the downregulation of the imprinted Dlk1-Dio3 locus, a complex genomic region containing protein-coding genes and non-coding RNAs that has been linked to tumor malignancy in lung cancer patients. The Dlk1- Dio3 locus repression mediated by Snail was found to occur specifically in several populations of tumor-infiltrating immune cells. It could be reproduced in primary splenocytes upon ex vivo culture with conditioned medium from Snail-expressing cancer cell lines, which suggests that a Snail-induced soluble factor secreted by the cancer cells mediates the Dlk1-Dio3 locus repression in immune cells, particularly in lymphocytes. Our findings furthermore point towards the contribution of Snail to an inflammatory tumor microenvironment, which is in line with our previous report of the Snail-mediated recruitment of pro-tumorigenic neutrophils to the lung tumors. This underlines an important role for Snail in influencing the immune compartment of lung tumors and thus contributing to disease progression.

2018