In1-ghrelin splicing variant is associated with reduced disease-free survival of breast cancer patients and increases malignancy of breast cancer cells lines

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dc.contributor.author Rincón-Fernández, David
dc.contributor.author Culler, Michael D.
dc.contributor.author Tsomaia, Natia
dc.contributor.author Moreno-Bueno, Gema
dc.contributor.author Luque, Raúl M.
dc.contributor.author Gahete, Manuel D.
dc.contributor.author Castaño, Justo P.
dc.contributor.other UAM. Departamento de Bioquímica es_ES
dc.contributor.other Centro de Biología Molecular Severo Ochoa (CBM) es_ES
dc.date.accessioned 2018-10-04T16:49:17Z
dc.date.available 2018-10-04T16:49:17Z
dc.date.issued 2017-12-19
dc.identifier.citation Carcinogenesis 39.3 (2018): 447-457 en_US
dc.identifier.issn 0143-3334 (print) es_ES
dc.identifier.issn 1460-2180 (online) es_ES
dc.identifier.uri http://hdl.handle.net/10486/685264
dc.description OXFORD UNIVERSITY: This is a pre-copyedited, author-produced version of an article accepted for publication in Carcinogenesis following peer review. The version of record David Rincón-Fernández, Michael D Culler, Natia Tsomaia, Gema Moreno-Bueno, Raúl M Luque, Manuel D Gahete, Justo P Castaño; In1-ghrelin splicing variant is associated with reduced disease-free survival of breast cancer patients and increases malignancy of breast cancer cells lines, Carcinogenesis, Volume 39, Issue 3, 8 March 2018, Pages 447–457, https://doi.org/10.1093/carcin/bgx146 en_US
dc.description.abstract Ghrelin gene generates several variants that regulate multiple pathophysiological functions, including tumor-related processes. In1-ghrelin is a splicing variant that was previously shown to be overexpressed in breast cancer (BCa), where it correlated with proliferation markers; however, its possible association with clinical outcome of BCa patients and underlying mechanisms are still unknown. To address this issue, expression levels and clinical associations of In1-ghrelin were analyzed in a cohort of 117 BCa samples. Additionally, a battery of cellular and molecular assays was implemented using two BCa cell lines (MCF-7 and MDA-MB-231), wherein the role of In1-ghrelin on proliferation, migration, dedifferentiation and signaling pathways was explored. The results generated revealed that high expression of In1-ghrelin in BCa samples was associated with lymph node metastasis and reduced disease-free survival. Indeed, In1-ghrelin overexpression stimulated proliferation and migration in MCF-7 and MDA-MB-231 cells. Similar results were found by treating MDA-MB-231 and MCF-7 with In1- ghrelin-derived peptides. Conversely, In1-ghrelin silencing decreased proliferation and migration capacities of MDA-MB-231. Furthermore, In1-ghrelin (but not ghrelin) overexpression increased the capacity to form mammospheres in both cell lines. These effects could be associated with activation of MAPK-ERK, Jag1/Notch, Wnt/β-catenin and/or TGF-β1 pathways. Altogether, our data indicate that In1-ghrelin could play relevant functional roles in the regulation of BCa development and progression and may provide insights to identify novel biomarkers and new therapeutic approaches for this pathology. en_US
dc.description.sponsorship BIO-0139, CTS-1406, PI-639-2012, PI-0541-2013 (Junta de Andalucia), BFU2013-43282-R, BFU2016-80360-R (MINECO), PI13-00651, PI16/00264 (Proyectos de Investigación en Salud FIS, funded by Instituto de Salud Carlos III), GETNE Grant 2014, Merck Serono Grant 2013 and CIBERobn (to RML and JPC); PI13/00132, RETICC RD12/0036/0007, CIBERonc and S2010/BMD-2303 (to GMB) en_US
dc.format.extent 32 pag. es_ES
dc.format.mimetype application/pdf en
dc.language.iso eng en
dc.publisher Oxford University Press en_US
dc.relation.ispartof Carcinogenesis en_US
dc.rights © The Author(s) 2018. Published by Oxford University Press. All rights reserved en_US
dc.subject.other In1-ghrelin en_US
dc.subject.other Splicing variant en_US
dc.subject.other Breast cancer en_US
dc.subject.other Malignancy en_US
dc.subject.other Survival en_US
dc.title In1-ghrelin splicing variant is associated with reduced disease-free survival of breast cancer patients and increases malignancy of breast cancer cells lines en_US
dc.type article en
dc.subject.eciencia Medicina es_ES
dc.date.embargoend 2018-12-19
dc.relation.publisherversion http://doi.org/10.1093/carcin/bgx146 es_ES
dc.identifier.doi 10.1093/carcin/bgx146 es_ES
dc.identifier.publicationfirstpage 447 es_ES
dc.identifier.publicationissue 3 es_ES
dc.identifier.publicationlastpage 457 es_ES
dc.identifier.publicationvolume 39 es_ES
dc.relation.projectID Gobierno de España. BFU2013-43282-R es_ES
dc.relation.projectID Gobierno de España. BFU2016-80360-R es_ES
dc.relation.projectID Gobierno de España. PI13-00651 es_ES
dc.relation.projectID Gobierno de España. PI16/00264 es_ES
dc.relation.projectID Comunidad de Madrid. S2010/BMD-2303/RECARE es_ES
dc.type.version info:eu-repo/semantics/acceptedVersion en
dc.rights.accessRights openAccess en


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