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Gasdermin-B Promotes Invasion and Metastasis in Breast Cancer Cells

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 over-expression has been related to tumor progression. At least four splicing...

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Autores principales: Hergueta-Redondo, Marta, Sarrió, David, Molina-Crespo, Ángela, Megias, Diego, Mota, Alba, Rojo-Sebastian, Alejandro, García-Sanz, Pablo, Morales, Saleta, Abril, Sandra, Cano, Amparo, Peinado, Héctor, Moreno-Bueno, Gema
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3967990/
https://www.ncbi.nlm.nih.gov/pubmed/24675552
http://dx.doi.org/10.1371/journal.pone.0090099
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author Hergueta-Redondo, Marta
Sarrió, David
Molina-Crespo, Ángela
Megias, Diego
Mota, Alba
Rojo-Sebastian, Alejandro
García-Sanz, Pablo
Morales, Saleta
Abril, Sandra
Cano, Amparo
Peinado, Héctor
Moreno-Bueno, Gema
author_facet Hergueta-Redondo, Marta
Sarrió, David
Molina-Crespo, Ángela
Megias, Diego
Mota, Alba
Rojo-Sebastian, Alejandro
García-Sanz, Pablo
Morales, Saleta
Abril, Sandra
Cano, Amparo
Peinado, Héctor
Moreno-Bueno, Gema
author_sort Hergueta-Redondo, Marta
collection PubMed
description 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 over-expression 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.
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spelling pubmed-39679902014-04-01 Gasdermin-B Promotes Invasion and Metastasis in Breast Cancer Cells Hergueta-Redondo, Marta Sarrió, David Molina-Crespo, Ángela Megias, Diego Mota, Alba Rojo-Sebastian, Alejandro García-Sanz, Pablo Morales, Saleta Abril, Sandra Cano, Amparo Peinado, Héctor Moreno-Bueno, Gema PLoS One Research Article 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 over-expression 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. Public Library of Science 2014-03-27 /pmc/articles/PMC3967990/ /pubmed/24675552 http://dx.doi.org/10.1371/journal.pone.0090099 Text en © 2014 Hergueta-Redondo et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Hergueta-Redondo, Marta
Sarrió, David
Molina-Crespo, Ángela
Megias, Diego
Mota, Alba
Rojo-Sebastian, Alejandro
García-Sanz, Pablo
Morales, Saleta
Abril, Sandra
Cano, Amparo
Peinado, Héctor
Moreno-Bueno, Gema
Gasdermin-B Promotes Invasion and Metastasis in Breast Cancer Cells
title Gasdermin-B Promotes Invasion and Metastasis in Breast Cancer Cells
title_full Gasdermin-B Promotes Invasion and Metastasis in Breast Cancer Cells
title_fullStr Gasdermin-B Promotes Invasion and Metastasis in Breast Cancer Cells
title_full_unstemmed Gasdermin-B Promotes Invasion and Metastasis in Breast Cancer Cells
title_short Gasdermin-B Promotes Invasion and Metastasis in Breast Cancer Cells
title_sort gasdermin-b promotes invasion and metastasis in breast cancer cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3967990/
https://www.ncbi.nlm.nih.gov/pubmed/24675552
http://dx.doi.org/10.1371/journal.pone.0090099
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