Gasdermin-B promotes invasion and metastasis in breast cancer cells

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dc.contributor.author Hergueta-Redondo, Marta
dc.contributor.author Sarrió, David
dc.contributor.author Molina-Crespo, Ángela
dc.contributor.author Megìas, Diego
dc.contributor.author Mota, Alba
dc.contributor.author Rojo-Sebastián, Alejandro
dc.contributor.author García-Sanz, Pablo
dc.contributor.author Morales, Saleta
dc.contributor.author Abril, Sandra
dc.contributor.author Cano, Amparo
dc.contributor.author Peinado, Héctor
dc.contributor.author Moreno-Bueno, Gema
dc.contributor.other UAM. Departamento de Bioquímica es_ES
dc.date.accessioned 2015-05-12T11:13:24Z
dc.date.available 2015-05-12T11:13:24Z
dc.date.issued 2014-03-27
dc.identifier.citation Plos One 9.3 (2014): e90099 en_US
dc.identifier.issn 1932-6203 (online) en_US
dc.identifier.uri http://hdl.handle.net/10486/666134
dc.description.abstract Gasdermin B (GSDMB) belongs to the Gasdermin protein family that comprises four members (GSDMA-D). Gasdermin B expression has been detected in some tumor types such as hepatocarcinomas, gastric and cervix cancers; and its overexpression has been related to tumor progression. At least four splicing isoforms of GSDMB have been identified, which may play differential roles in cancer. However, the implication of GSDMB in carcinogenesis and tumor progression is not well understood. Here, we uncover for the first time the functional implication of GSDMB in breast cancer. Our data shows that high levels of GSDMB expression is correlated with reduced survival and increased metastasis in breast cancer patients included in an expression dataset (>1,000 cases). We demonstrate that GSDMB is upregulated in breast carcinomas compared to normal breast tissue, being the isoform 2 (GSDMB-2) the most differentially expressed. In order to evaluate the functional role of GSDMB in breast cancer two GSDMB isoforms were studied (GSDMB-1 and GSDMB-2). The overexpression of both isoforms in the MCF7 breast carcinoma cell line promotes cell motility and invasion, while its silencing in HCC1954 breast carcinoma cells decreases the migratory and invasive phenotype. Importantly, we demonstrate that both isoforms have a differential role on the activation of Rac-1 and Cdc-42 Rho-GTPases. Moreover, our data support that GSMDB-2 induces a pro-tumorigenic and pro-metastatic behavior in mouse xenograft models as compared to GSDMB-1. Finally, we observed that although both GSDMB isoforms interact in vitro with the chaperone Hsp90, only the GSDMB-2 isoform relies on this chaperone for its stability. Taken together, our results provide for the first time evidences that GSDMB-2 induces invasion, tumor progression and metastasis in MCF7 cells and that GSDMB can be considered as a new potential prognostic marker in breast cancer en_US
dc.description.sponsorship This work was supported by grants from the Spanish Ministry of Science and Innovation, MICINN (SAF2007-63075 and SAF2010-20175), AVON Foundation 2012, Comunidad de Madrid (S2010/BMD-2302), AECC network 2011, Instituto de Salud Carlos III (ISCIII) (PI13_00132) to GMB and Breast Network from ISCIII RD12036/0007 to AC. MHR has been funded by a predoctoral contract associated to SAF2007-63075 and now has a postdoc contract from S2010/BMD- 23. DS and PGS are funded by postdoc contracts from the AECC Scientific Foundation, AM is funded by a predoctoral fellowship from MECD; ACM is funded by ISCIII RD12036/0007. Dr HP’s work is supported by the Melanoma Research Alliance, Pediatric Oncology Experimental Therapeutics Investigators Consortium, The Nancy C. and Daniel P. Paduano Foundation, The Manning Foundation, NCI (U01 CA169538, RO1 CA169416-01) and the DoD (BC123187, BC121988 en_US
dc.format.extent 15 pag. es_ES
dc.format.mimetype application/pdf es_ES
dc.language.iso eng en
dc.publisher Public Library of Science en_US
dc.relation.ispartof Plos One en_US
dc.rights © 2014 Hergueta-Redondo et al. en
dc.subject.other breast cancer en_US
dc.subject.other cell invasion en_US
dc.subject.other metastasis en_US
dc.subject.other protein expression en_US
dc.subject.other in vitro study en_US
dc.title Gasdermin-B promotes invasion and metastasis in breast cancer cells en_US
dc.type article en
dc.subject.eciencia Medicina es_ES
dc.identifier.doi 10.1371/journal.pone.0090099 es_ES
dc.identifier.publicationfirstpage e90099 es_ES
dc.identifier.publicationissue 3 es_ES
dc.identifier.publicationlastpage e90099 es_ES
dc.identifier.publicationvolume 9 es_ES
dc.relation.projectID Comunidad de Madrid. S2010/BMD-2303/RECARE es_ES
dc.relation.projectID Gobierno de España. SAF2007-63075 es_ES
dc.relation.projectID Gobierno de España. SAF2010-20175 es_ES
dc.relation.projectID Gobierno de España. PI13/00132 es_ES
dc.type.version info:eu-repo/semantics/publishedVersion en
dc.rights.cc Reconocimiento es_ES
dc.rights.accessRights openAccess en
dc.authorUAM Sarrio López, José David (264833)


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