Inhibidores del factor prometastásico snail-1

La presente invención se refiere al uso de inhibidores del factor prometastásico snail-1 para la elaboración de un medicamento para el tratamiento de la metástasis pulmonar.Peer reviewedConsejo Superior de Investigaciones Científicas (España), Fundació IMIMA1 Solicitud de patente con informe sobre el estado de la técnic

Estudio funcional del Adjetivo Conexo en 'El mundo de Juan Lobón

En el presente trabajo se realiza el estudio funcional de los adjetivos que aparecen en la novela de Luis Berenguer, titulada El Mundo De Juan Lobón. Concretamente, centraremos nuestro interés en los subtipos de Adjetivo Conexo Aditamento Atributivo y Atributo del Implemento. Clasificamos los casos encontrados atendiendo a las distintas categorías o construcciones que puedan realizar dichas funciones. Nuestro trabajo no pretende crear teoría nueva relativa a estos conceptos, sino más bien corroborar mediante los usos de la lengua en la obra de Berenguer la frecuencia de su utilización.In this paper we are going to carry out the functional study of the adjectives appearing on Luis Berenguer's novel, entitled El Mundo De Juan Lobon. Specifically, we study that kind of adjectives called "Adjetivo Conexo Aditamento Atributivo" and "Atributo del Implemento". We classify the examples attending to the different categories or structures that can carry out the funtions mentioned above. Our paper does not seek to create a new theory related to these concepts, but to corroborate with the uses of speech in Berenguer's work the frequency of their use.Avec notre travail on va faire 1' étude fonctionnel des adjectives du roman de Luis Berenguer El Mundo De Juan Lohôn. Concrètement on va centrer notre intérêt aux subtipes d'Adjectif-conexe "Aditamento Atributivo" et "Atributo del Implemento". On fait la clasification des exemples trouvés en attendant aux diverses catégories ou constructions qui peuvent réaliser ces fontions. Notre travail ne veut pas créer théorie relative a ces concepts, mais mieux, corroborer à travers les usages de la langue au texte de Berenguer, la fréquence de son utilisation

Caracterización Proteómica del papel de Snail1 en diferenciación de fibroblastos murinos mediante SILAC

Comunicaciones a congreso

Protumorigenic effects of Snail-expression fibroblasts on colon cancer cells

et al.Snail1 is a transcriptional factor that plays an important role in epithelial–mesenchymal transition and in the acquisition of invasive properties by epithelial cells. In colon tumors, Snail1 expression in the stroma correlates with lower specific survival of cancer patients. However, the role(s) of Snail1 expression in stroma and its association with patients' survival have not been determined. We used human primary carcinoma-associated fibroblasts (CAFs) or normal fibroblasts (NFs) and fibroblast cell lines to analyze the effects of Snail1 expression on the protumorigenic capabilities in colon cancer cells. Snail1 expression was higher in CAFs than in NFs and, as well as α-SMA, a classic marker of activated CAFs. Moreover, in tumor samples from 50 colon cancer patients, SNAI1 expression was associated with expression of other CAF markers, such as α-SMA and fibroblast activation protein. Interestingly, coculture of CAFs with colon cells induced a significant increase in epithelial cell migration and proliferation, which was associated with endogenous SNAI1 expression levels. Ectopic manipulation of Snail1 in fibroblasts demonstrated that Snail1 expression controlled migration as well as proliferation of cocultured colon cancer cells in a paracrine manner. Furthermore, expression of Snail1 in fibroblasts was required for the coadjuvant effect of these cells on colon cancer cell growth and invasion when coxenografted in nude mice. Finally, cytokine profile changes, particularly MCP-3 expression, in fibroblasts are put forward as mediators of Snail1-derived effects on colon tumor cell migration. In summary, these studies demonstrate that Snail1 is necessary for the protumorigenic effects of fibroblasts on colon cancer cells.This research was supported by the PI12/02037, Fundación Científica AECC, SAF2010-20750, S2010/BMD-2344, RTICC-RD12/0036/0041 and by the Fundación Banco Santander. Antonio García de Herreros’ laboratory was supported by RTICC-RD12/0036/0005 and SAF 2010-16089. Ma Jesús Larriba’s laboratory was supported by RD12/0036/0021. Cristina Peña and José Miguel García are recipients of Miguel Servet Contracts from the Instituto de Salud Carlos III.Peer reviewe

Valoración del impacto de recursos audiovisuales sobre Asia

Creación de recursos docentes audiovisuales sobre Asia, de carácter semipresencial, y valoración de su impacto y calidad, con el objetivo reforzar la enseñanza del ámbito asiático en la enseñanza universitaria española en general y del UCM en particular

Snail1 transcription factor controls telomere transcription and integrity

Besides controlling epithelial-to-mesenchymal transition (EMT) and cell invasion, the Snail1 transcriptional factor also provides cells with cancer stem cell features. Since telomere maintenance is essential for stemness, we have examined the control of telomere integrity by Snail1. Fluorescence in situ hybridization (FISH) analysis indicates that Snail1-depleted mouse mesenchymal stem cells (MSC) have both a dramatic increase of telomere alterations and shorter telomeres. Remarkably, Snail1-deficient MSC present higher levels of both telomerase activity and the long non-coding RNA called telomeric repeat-containing RNA (TERRA), an RNA that controls telomere integrity. Accordingly, Snail1 expression downregulates expression of the telomerase gene (TERT) as well as of TERRA 2q, 11q and 18q. TERRA and TERT are transiently downregulated during TGF-induced EMT in NMuMG cells, correlating with Snail1 expression. Global transcriptome analysis indicates that ectopic expression of TERRA affects the transcription of some genes induced during EMT, such as fibronectin, whereas that of TERT does not modify those genes. We propose that Snail1 repression of TERRA is required not only for telomere maintenance but also for the expression of a subset of mesenchymal genes

RhoA–ROCK and p38MAPK-MSK1 mediate vitamin D effects on gene expression, phenotype, and Wnt pathway in colon cancer cells

The active vitamin D metabolite 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) inhibits proliferation and promotes differentiation of colon cancer cells through the activation of vitamin D receptor (VDR), a transcription factor of the nuclear receptor superfamily. Additionally, 1,25(OH)2D3 has several nongenomic effects of uncertain relevance. We show that 1,25(OH)2D3 induces a transcription-independent Ca2+ influx and activation of RhoA–Rho-associated coiled kinase (ROCK). This requires VDR and is followed by activation of the p38 mitogen-activated protein kinase (p38MAPK) and mitogen- and stress-activated kinase 1 (MSK1). As shown by the use of chemical inhibitors, dominant-negative mutants and small interfering RNA, RhoA–ROCK, and p38MAPK-MSK1 activation is necessary for the induction of CDH1/E-cadherin, CYP24, and other genes and of an adhesive phenotype by 1,25(OH)2D3. RhoA–ROCK and MSK1 are also required for the inhibition of Wnt–β-catenin pathway and cell proliferation. Thus, the action of 1,25(OH)2D3 on colon carcinoma cells depends on the dual action of VDR as a transcription factor and a nongenomic activator of RhoA–ROCK and p38MAPK-MSK1

Novel Snail1 Target Proteins in Human Colon Cancer Identified by Proteomic Analysis

This is an open-access article distributed under the terms of the Creative Commons Attribution License.-- et al.[Background]: The transcription factor Snail1 induces epithelial-to-mesenchymal transition (EMT), a process responsible for the acquisition of invasiveness during tumorigenesis. Several transcriptomic studies have reported Snail1-regulated genes in different cell types, many of them involved in cell adhesion. However, only a few studies have used proteomics as a tool for the characterization of proteins mediating EMT. [Methodology/Principal Findings]: We identified by proteomic analysis using 2D-DIGE electrophoresis combined with MALDI-TOF-TOF and ESI-linear ion trap mass spectrometry a number of proteins with variable functions whose expression is modulated by Snail1 in SW480-ADH human colon cancer cells. Validation was performed by Western blot and immunofluorescence analyses. Snail1 repressed several members of the 14-3-3 family of phosphoserine/phosphothreonine binding proteins and also the expression of the Proliferation-associated protein 2G4 (PA2G4) that was mainly localized at the nuclear Cajal bodies. In contrast, the expression of two proteins involved in RNA processing, the Cleavage and polyadenylation specificity factor subunit 6 (CPSF6) and the Splicing factor proline/glutamine-rich (SFPQ), was higher in Snail1-expressing cells than in controls. The regulation of 14-3-3 epsilon, 14-3-3 tau, 14-3-3 zeta and PA2G4 by Snail1 was reproduced in HT29 colon cancer cells. In addition, we found an inverse correlation between 14-3-3 sigma and Snail1 expression in human colorectal tumors. [Conclusions/Significance]: We have identified a set of novel Snail1 target proteins in colon cancer that expand the cellular processes affected by Snail1 and thus its relevance for cell function and phenotype.Peer reviewe