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DC Field | Value | Language |
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dc.contributor.author | Lluís Duquez, Josep Maria | - |
dc.contributor.author | Llacuna Durán, Laura | - |
dc.contributor.author | von Montfort, Claudia | - |
dc.contributor.author | Bárcena, Cristina | - |
dc.contributor.author | Enrich Bastús, Carles | - |
dc.contributor.author | Morales Muñoz, Albert | - |
dc.contributor.author | Fernández-Checa Torres, José Carlos | - |
dc.date.accessioned | 2013-05-06T08:07:22Z | - |
dc.date.available | 2013-05-06T08:07:22Z | - |
dc.date.issued | 2009-11-26 | - |
dc.identifier.issn | 1932-6203 | - |
dc.identifier.uri | http://hdl.handle.net/2445/42350 | - |
dc.description.abstract | Abstract Background: Hypoxia-mediated HIF-1a stabilization and NF-kB activation play a key role in carcinogenesis by fostering cancer cell survival, angiogenesis and tumor invasion. Gangliosides are integral components of biological membranes with an increasingly recognized role as signaling intermediates. In particular, ganglioside GD3 has been characterized as a proapoptotic lipid effector by promoting cell death signaling and suppression of survival pathways. Thus, our aim was to analyze the role of GD3 in hypoxia susceptibility of hepatocarcinoma cells and in vivo tumor growth. Methodology/Principal Findings: We generated and characterized a human hepatocarcinoma cell line stably expressing GD3 synthase (Hep3B-GD3), which catalyzes the synthesis of GD3 from GM3. Despite increased GD3 levels (2-3 fold), no significant changes in cell morphology or growth were observed in Hep3B-GD3 cells compared to wild type Hep3B cells under normoxia. However, exposure of Hep3B-GD3 cells to hypoxia (2% O2) enhanced reactive oxygen species (ROS) generation, resulting in decreased cell survival, with similar findings observed in Hep3B cells exposed to increasing doses of exogenous GD3. In addition, hypoxia-induced c-Src phosphorylation at tyrosine residues, NF-kB activation and subsequent expression of Mn-SOD were observed in Hep3B cells but not in Hep3B-GD3 cells. Moreover, MnTBAP, an antioxidant with predominant SOD mimetic activity, reduced ROS generation, protecting Hep3B-GD3 cells from hypoxia-induced death. Finally, lower tumor growth, higher cell death and reduced Mn-SOD expression were observed in Hep3B-GD3 compared to Hep3B tumor xenografts. Conclusion: These findings underscore a role for GD3 in hypoxia susceptibility by disabling the c-Src/NF-kB survival pathway resulting in lower Mn-SOD expression, which may be of relevance in hepatocellular carcinoma therapy. | - |
dc.format.extent | 11 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | Public Library of Science (PLoS) | - |
dc.relation.isformatof | Reproducció del document publicat a: http://dx.doi.org/10.1371/journal.pone.0008059 | - |
dc.relation.ispartof | PLoS One, 2009, vol. 4, num. 11, p. e8059 | - |
dc.relation.uri | http://dx.doi.org/10.1371/journal.pone.0008059 | - |
dc.rights | cc-by (c) Lluis, J.M. et al., 2009 | - |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es | - |
dc.source | Articles publicats en revistes (Biomedicina) | - |
dc.subject.classification | Càncer de fetge | - |
dc.subject.classification | Carcinogènesi | - |
dc.subject.classification | Teràpia genètica | - |
dc.subject.classification | Transport biològic | - |
dc.subject.other | Liver cancer | - |
dc.subject.other | Carcinogenesis | - |
dc.subject.other | Gene therapy | - |
dc.subject.other | Biological transport | - |
dc.title | GD3 Synthase Overexpression Sensitizes Hepatocarcinoma Cells to Hypoxia and Reduces Tumor Growth by Suppressing the cSrc/NF-κB Survival Pathway | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.identifier.idgrec | 584319 | - |
dc.date.updated | 2013-05-06T08:07:22Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.pmid | 19956670 | - |
Appears in Collections: | Articles publicats en revistes (Biomedicina) |
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