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61.
62.
PARP-1 Regulates Metastatic Melanoma through Modulation of Vimentin-induced Malignant Transformation
María Isabel Rodríguez Andreína Peralta-Leal Francisco O'Valle José Manuel Rodriguez-Vargas Ariannys Gonzalez-Flores Jara Majuelos-Melguizo Laura López Santiago Serrano Antonio García de Herreros Juan Carlos Rodríguez-Manzaneque Rubén Fernández Raimundo G. del Moral José Mariano de Almodóvar F. Javier Oliver 《PLoS genetics》2013,9(6)
PARP inhibition can induce anti-neoplastic effects when used as monotherapy or in combination with chemo- or radiotherapy in various tumor settings; however, the basis for the anti-metastasic activities resulting from PARP inhibition remains unknown. PARP inhibitors may also act as modulators of tumor angiogenesis. Proteomic analysis of endothelial cells revealed that vimentin, an intermediary filament involved in angiogenesis and a specific hallmark of EndoMT (endothelial to mesenchymal transition) transformation, was down-regulated following loss of PARP-1 function in endothelial cells. VE-cadherin, an endothelial marker of vascular normalization, was up-regulated in HUVEC treated with PARP inhibitors or following PARP-1 silencing; vimentin over-expression was sufficient to drive to an EndoMT phenotype. In melanoma cells, PARP inhibition reduced pro-metastatic markers, including vasculogenic mimicry. We also demonstrated that vimentin expression was sufficient to induce increased mesenchymal/pro-metastasic phenotypic changes in melanoma cells, including ILK/GSK3-β-dependent E-cadherin down-regulation, Snail1 activation and increased cell motility and migration. In a murine model of metastatic melanoma, PARP inhibition counteracted the ability of melanoma cells to metastasize to the lung. These results suggest that inhibition of PARP interferes with key metastasis-promoting processes, leading to suppression of invasion and colonization of distal organs by aggressive metastatic cells. 相似文献
63.
Hermann Cuntz Friedrich Forstner Bettina Schnell Georg Ammer Shamprasad Varija Raghu Alexander Borst 《PloS one》2013,8(8)
Important brain functions need to be conserved throughout organisms of extremely varying sizes. Here we study the scaling properties of an essential component of computation in the brain: the single neuron. We compare morphology and signal propagation of a uniquely identifiable interneuron, the HS cell, in the blowfly (Calliphora) with its exact counterpart in the fruit fly (Drosophila) which is about four times smaller in each dimension. Anatomical features of the HS cell scale isometrically and minimise wiring costs but, by themselves, do not scale to preserve the electrotonic behaviour. However, the membrane properties are set to conserve dendritic as well as axonal delays and attenuation as well as dendritic integration of visual information. In conclusion, the electrotonic structure of a neuron, the HS cell in this case, is surprisingly stable over a wide range of morphological scales. 相似文献
64.
Injection of tumor cells in mice more than 30 years ago resulted in the discovery of an epithelial antigen, later defined as a cell adhesion molecule (EpCAM). Although EpCAM has since evoked significant interest as a target in cancer therapy, mechanistic insights on the functions of this glycoprotein have been emerging only very recently. This may have been caused by the multitude of functions attributed to the glycoprotein, its localization at different subcellular sites and complex posttranslational modifications. Here, we review how EpCAM modifies cell–cell contact adhesion strength and tissue plasticity, and how it regulates cell proliferation and differentiation. Major knowledge derived from human diseases will be highlighted: Mutant EpCAM that is absent from the cell surface leads to fatal intestinal abnormalities (congenital tufting enteropathy). EpCAM-mediated cell proliferation in cancer may result from signaling (i) via regulated intramembrane proteolysis and/or (ii) the localization and association with binding partners in specialized membrane microdomains. New insight in EpCAM signaling will help to develop optimized cancer therapies and open new avenues in the field of regenerative medicine. 相似文献
65.
Ailec Ho‐Plagaro Concepcin Santiago‐Fernandez Cristina Rodríguez‐Díaz Carlos Lopez‐Gmez Sara Garcia‐Serrano Francisca Rodríguez‐Pacheco Sergio Valdes Alberto Rodríguez‐Caete Guillermo Alcaín‐Martínez Natalia Ruiz‐Santana Luis Vzquez‐Pedreo Eduardo García‐Fuentes 《Obesity (Silver Spring, Md.)》2020,28(9):1708-1717
66.
Blanca Domenech‐Ximenos Victor Cuba Pepus Daunis‐i‐Estadella Santiago Thi‐Henestrosa Francisco Jaldo Carles Biarnes Xavier Molina Gemma Xifra Wifredo Ricart Anton Bardera Imma Boada Marco Essig Salvador Pedraza Massimo Federici Jos Manuel Fernndez‐Real Josep Puig 《Obesity (Silver Spring, Md.)》2020,28(9):1663-1670
67.
Francesco Rovero Jorge Ahumada Patrick A. Jansen Douglas Sheil Patricia Alvarez Kelly Boekee Santiago Espinosa Marcela Guimarães Moreira Lima Emanuel H. Martin Timothy G. O'Brien Julia Salvador Fernanda Santos Melissa Rosa Alexander Zvoleff Chris Sutherland Simone Tenan 《Ecography》2020,43(1):75-84
The understanding of global diversity patterns has benefitted from a focus on functional traits and how they relate to variation in environmental conditions among assemblages. Distant communities in similar environments often share characteristics, and for tropical forest mammals, this functional trait convergence has been demonstrated at coarse scales (110–200 km resolution), but less is known about how these patterns manifest at fine scales, where local processes (e.g. habitat features and anthropogenic activities) and biotic interactions occur. Here, we used standardized camera trapping data and a novel analytical method that accounts for imperfect detection to assess how the functional composition of terrestrial mammal communities for two traits – trophic guild and body mass – varies across 16 protected areas in tropical forests and three continents, in relation to the extent of protected habitat and anthropogenic pressures. We found that despite their taxonomic differences, communities generally have a consistent trophic guild composition, and respond similarly to these factors. Insectivores were found to be sensitive to the size of protected habitat and surrounding human population density. Body mass distribution varied little among communities both in terms of central tendency and spread, and interestingly, community average body mass declined with proximity to human settlements. Results indicate predicted trait convergence among assemblages at the coarse scale reflects consistent functional composition among communities at the local scale, suggesting that broadly similar habitats and selective pressures shaped communities with similar trophic strategies and responses to drivers of change. These similarities provide a foundation for assessing assemblages under anthropogenic threats and sharing conservation measures. 相似文献
68.
Loss of function of Arabidopsis NADP‐malic enzyme 1 results in enhanced tolerance to aluminum stress
69.
70.
Studies have found that mutant, misfolded superoxide dismutase [Cu–Zn] (SOD1) can convert wild type SOD1 (wtSOD1) in a prion-like fashion, and that misfolded wtSOD1 can be propagated by release and uptake of protein aggregates. In developing a prion-like mechanism for this propagation of SOD1 misfolding we have previously shown how enervation of the SOD1 electrostatic loop (ESL), caused by the formation of transient non-obligate SOD1 oligomers, can lead to an experimentally observed gain of interaction (GOI) that results in the formation of SOD1 amyloid-like filaments. It has also been shown that freedom of ESL motion is essential to catalytic function. This work investigates the possibility that restricting ESL mobility might not only compromise superoxide catalytic activity but also serve to promote the peroxidase activity of SOD1, thus implicating the formation of SOD1 oligomers in both protein misfolding and in protein oxidation. 相似文献