In1-ghrelin, a splice variant of ghrelin gene, is associated with the evolution and aggressiveness of human neuroendocrine tumors: Evidence from clinical, cellular and molecular parameters
Ghrelin system comprises a complex family of peptides, receptors (GHSRs), and modifying enzymes [e.g. ghrelin-O-acyl-transferase (GOAT)] that control multiple pathophysiological processes. Aberrant alternative splicing is an emerging cancer hallmark that generates altered proteins with tumorigenic c...
| Autores: | , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2015 |
| País: | España |
| Institución: | Universidad Autónoma de Madrid |
| Repositorio: | Biblos-e Archivo. Repositorio Institucional de la UAM |
| Idioma: | inglés |
| OAI Identifier: | oai:repositorio.uam.es:10486/669506 |
| Acceso en línea: | http://hdl.handle.net/10486/669506 https://dx.doi.org/10.18632/oncotarget.4316 |
| Access Level: | acceso abierto |
| Palabra clave: | ghrelin system splicing variant neuroendocrine tumors aggressiveness clinical evolution Medicina |
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In1-ghrelin, a splice variant of ghrelin gene, is associated with the evolution and aggressiveness of human neuroendocrine tumors: Evidence from clinical, cellular and molecular parametersLuque, Raúl M.Sampedro Núñez, Miguel AntonioGahete, Manuel D.Ramos-Levi, Ana M.Ibáñez Costa, AlejandroRivero-Cortés, EstherSerrano-Somavilla, AnaAdrados, MagdalenaCuller, Michael D.Castaño, Justo P.Marazuela Azpiroz, Mónicaghrelin systemsplicing variantneuroendocrine tumorsaggressivenessclinical evolutionMedicinaGhrelin system comprises a complex family of peptides, receptors (GHSRs), and modifying enzymes [e.g. ghrelin-O-acyl-transferase (GOAT)] that control multiple pathophysiological processes. Aberrant alternative splicing is an emerging cancer hallmark that generates altered proteins with tumorigenic capacity. Indeed, In1-ghrelin and truncated-GHSR1b splicing variants can promote development/ progression of certain endocrine-related cancers. Here, we determined the expression levels of key ghrelin system components in neuroendocrine tumor (NETs) and explored their potential functional role. Twenty-six patients with NETs were prospectively/retrospectively studied [72 samples from primary and metastatic tissues (30 normal/42 tumors)] and clinical data were obtained. The role of In1-ghrelin in aggressiveness was studied in vitro using NET cell lines (BON-1/QGP-1). In1-ghrelin, GOAT and GHSR1a/1b expression levels were elevated in tumoral compared to normal/adjacent tissues. Moreover, In1-ghrelin, GOAT, and GHSR1b expression levels were positively correlated within tumoral, but not within normal/adjacent samples, and were higher in patients with progressive vs. with stable/cured disease. Finally, In1-ghrelin increased aggressiveness (e.g. proliferation/migration) of NET cells. Altogether, our data strongly suggests a potential implication of ghrelin system in the pathogenesis and/or clinical outcome of NETs, and warrant further studies on their possible value for the future development of molecular biomarkers with diagnostic/prognostic/therapeutic valueThis work has received the following grants: Proyectos de Investigación en Salud (FIS) PI13–01414, and PIE-0041 (funded by Instituto de Salud Carlos III) and S2011/BMD-2328 TIRONET (funded by Comunidad de Madrid) (to MM). BIO-0139, CTS-1406, PI-0639–2012 (funded by Junta de Andalucía), Proyectos de Investigación en Salud (FIS) PI13–00651 (funded by Instituto de Salud Carlos III), BFU2013–43282-R (funded by Ministerio de Economía y Competitividad), CIBERobn and Ayuda Merck Serono 2013 (to RML and JPC). Fellowship CTS-5051 (to AIC). “Sara Borrell” program CD11/00276 (to MDG)Impact JournalsDepartamento de MedicinaFacultad de Medicina20152015-08-14research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10486/669506https://dx.doi.org/10.18632/oncotarget.4316reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/6695062026-06-23T12:46:27Z |
| dc.title.none.fl_str_mv |
In1-ghrelin, a splice variant of ghrelin gene, is associated with the evolution and aggressiveness of human neuroendocrine tumors: Evidence from clinical, cellular and molecular parameters |
| title |
In1-ghrelin, a splice variant of ghrelin gene, is associated with the evolution and aggressiveness of human neuroendocrine tumors: Evidence from clinical, cellular and molecular parameters |
| spellingShingle |
In1-ghrelin, a splice variant of ghrelin gene, is associated with the evolution and aggressiveness of human neuroendocrine tumors: Evidence from clinical, cellular and molecular parameters Luque, Raúl M. ghrelin system splicing variant neuroendocrine tumors aggressiveness clinical evolution Medicina |
| title_short |
In1-ghrelin, a splice variant of ghrelin gene, is associated with the evolution and aggressiveness of human neuroendocrine tumors: Evidence from clinical, cellular and molecular parameters |
| title_full |
In1-ghrelin, a splice variant of ghrelin gene, is associated with the evolution and aggressiveness of human neuroendocrine tumors: Evidence from clinical, cellular and molecular parameters |
| title_fullStr |
In1-ghrelin, a splice variant of ghrelin gene, is associated with the evolution and aggressiveness of human neuroendocrine tumors: Evidence from clinical, cellular and molecular parameters |
| title_full_unstemmed |
In1-ghrelin, a splice variant of ghrelin gene, is associated with the evolution and aggressiveness of human neuroendocrine tumors: Evidence from clinical, cellular and molecular parameters |
| title_sort |
In1-ghrelin, a splice variant of ghrelin gene, is associated with the evolution and aggressiveness of human neuroendocrine tumors: Evidence from clinical, cellular and molecular parameters |
| dc.creator.none.fl_str_mv |
Luque, Raúl M. Sampedro Núñez, Miguel Antonio Gahete, Manuel D. Ramos-Levi, Ana M. Ibáñez Costa, Alejandro Rivero-Cortés, Esther Serrano-Somavilla, Ana Adrados, Magdalena Culler, Michael D. Castaño, Justo P. Marazuela Azpiroz, Mónica |
| author |
Luque, Raúl M. |
| author_facet |
Luque, Raúl M. Sampedro Núñez, Miguel Antonio Gahete, Manuel D. Ramos-Levi, Ana M. Ibáñez Costa, Alejandro Rivero-Cortés, Esther Serrano-Somavilla, Ana Adrados, Magdalena Culler, Michael D. Castaño, Justo P. Marazuela Azpiroz, Mónica |
| author_role |
author |
| author2 |
Sampedro Núñez, Miguel Antonio Gahete, Manuel D. Ramos-Levi, Ana M. Ibáñez Costa, Alejandro Rivero-Cortés, Esther Serrano-Somavilla, Ana Adrados, Magdalena Culler, Michael D. Castaño, Justo P. Marazuela Azpiroz, Mónica |
| author2_role |
author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Departamento de Medicina Facultad de Medicina |
| dc.subject.none.fl_str_mv |
ghrelin system splicing variant neuroendocrine tumors aggressiveness clinical evolution Medicina |
| topic |
ghrelin system splicing variant neuroendocrine tumors aggressiveness clinical evolution Medicina |
| description |
Ghrelin system comprises a complex family of peptides, receptors (GHSRs), and modifying enzymes [e.g. ghrelin-O-acyl-transferase (GOAT)] that control multiple pathophysiological processes. Aberrant alternative splicing is an emerging cancer hallmark that generates altered proteins with tumorigenic capacity. Indeed, In1-ghrelin and truncated-GHSR1b splicing variants can promote development/ progression of certain endocrine-related cancers. Here, we determined the expression levels of key ghrelin system components in neuroendocrine tumor (NETs) and explored their potential functional role. Twenty-six patients with NETs were prospectively/retrospectively studied [72 samples from primary and metastatic tissues (30 normal/42 tumors)] and clinical data were obtained. The role of In1-ghrelin in aggressiveness was studied in vitro using NET cell lines (BON-1/QGP-1). In1-ghrelin, GOAT and GHSR1a/1b expression levels were elevated in tumoral compared to normal/adjacent tissues. Moreover, In1-ghrelin, GOAT, and GHSR1b expression levels were positively correlated within tumoral, but not within normal/adjacent samples, and were higher in patients with progressive vs. with stable/cured disease. Finally, In1-ghrelin increased aggressiveness (e.g. proliferation/migration) of NET cells. Altogether, our data strongly suggests a potential implication of ghrelin system in the pathogenesis and/or clinical outcome of NETs, and warrant further studies on their possible value for the future development of molecular biomarkers with diagnostic/prognostic/therapeutic value |
| publishDate |
2015 |
| dc.date.none.fl_str_mv |
2015 2015-08-14 |
| dc.type.none.fl_str_mv |
research article http://purl.org/coar/resource_type/c_2df8fbb1 VoR http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| dc.identifier.none.fl_str_mv |
http://hdl.handle.net/10486/669506 https://dx.doi.org/10.18632/oncotarget.4316 |
| url |
http://hdl.handle.net/10486/669506 https://dx.doi.org/10.18632/oncotarget.4316 |
| dc.language.none.fl_str_mv |
Inglés eng |
| language_invalid_str_mv |
Inglés |
| language |
eng |
| dc.rights.none.fl_str_mv |
open access http://purl.org/coar/access_right/c_abf2 |
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info:eu-repo/semantics/openAccess |
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open access http://purl.org/coar/access_right/c_abf2 |
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openAccess |
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application/pdf |
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Impact Journals |
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Impact Journals |
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reponame:Biblos-e Archivo. Repositorio Institucional de la UAM instname:Universidad Autónoma de Madrid |
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Universidad Autónoma de Madrid |
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