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http://hdl.handle.net/2445/149449
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DC Field | Value | Language |
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dc.contributor.author | Camacho, Luz | - |
dc.contributor.author | Meca Cortés, Óscar | - |
dc.contributor.author | Abad, José Luis | - |
dc.contributor.author | García, Simón | - |
dc.contributor.author | Rubio, Nuria | - |
dc.contributor.author | Díaz Lorca, Maria Alba | - |
dc.contributor.author | Celià Terrassa, Toni | - |
dc.contributor.author | Cingolani, Francesca | - |
dc.contributor.author | Bermudo, Raquel | - |
dc.contributor.author | Fernández, Pedro L. | - |
dc.contributor.author | Blanco Fernández, Jerónimo | - |
dc.contributor.author | Delgado Cirilo, Antonio | - |
dc.contributor.author | Casas, Josefina | - |
dc.contributor.author | Fabriàs Domingo, Gemma | - |
dc.contributor.author | Thomson, Timothy M. | - |
dc.date.accessioned | 2020-02-05T15:33:30Z | - |
dc.date.available | 2020-02-05T15:33:30Z | - |
dc.date.issued | 2013-02-19 | - |
dc.identifier.issn | 0022-2275 | - |
dc.identifier.uri | http://hdl.handle.net/2445/149449 | - |
dc.description.abstract | Acid ceramidase (AC) catalyzes the hydrolysis of ceramide into sphingosine, in turn a substrate of sphingosine kinases that catalyze its conversion into the mitogenic sphingosine-1-phosphate. AC is expressed at high levels in several tumor types and has been proposed as a cancer therapeutic target. Using a model derived from PC-3 prostate cancer cells, the highly tumorigenic, metastatic, and chemoresistant clone PC-3/Mc expressed higher levels of the AC ASAH1 than the nonmetastatic clone PC-3/S. Stable knockdown of ASAH1 in PC-3/Mc cells caused an accumulation of ceramides, inhibition of clonogenic potential, increased requirement for growth factors, and inhibition of tumorigenesis and lung metastases. We developed de novo ASAH1 inhibitors, which also caused a dose-dependent accumulation of ceramides in PC-3/Mc cells and inhibited their growth and clonogenicity. Finally, immunohistochemical analysis of primary prostate cancer samples showed that higher levels of ASAH1 were associated with more advanced stages of this neoplasia. These observations confi rm ASAH1 as a therapeutic target in advanced and chemoresistant forms of prostate cancer and suggest that our new potent and specifi c AC inhibitors could act by counteracting critical growth properties of these highly aggressive tumor cells. | - |
dc.format.extent | 14 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | American Society for Biochemistry and Molecular Biology | - |
dc.relation.isformatof | Reproducció del document publicat a: https://doi.org/10.1194/jlr.M032375 | - |
dc.relation.ispartof | Journal of Lipid Research, 2013, vol. 54, p. 1207-1220 | - |
dc.relation.uri | https://doi.org/10.1194/jlr.M032375 | - |
dc.rights | (c) American Society for Biochemistry and Molecular Biology, 2013 | - |
dc.source | Articles publicats en revistes (Fonaments Clínics) | - |
dc.subject.classification | Càncer de pròstata | - |
dc.subject.classification | Metàstasi | - |
dc.subject.other | Prostate cancer | - |
dc.subject.other | Metastasis | - |
dc.title | Acid ceramidase as a therapeutic target in metastatic prostate cancer | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.identifier.idgrec | 639057 | - |
dc.date.updated | 2020-02-05T15:33:30Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.pmid | 23423838 | - |
Appears in Collections: | Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer) Articles publicats en revistes (Fonaments Clínics) Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica) |
Files in This Item:
File | Description | Size | Format | |
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639057.pdf | 1.54 MB | Adobe PDF | View/Open |
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