Reduced expression of the murine HLA-G homolog Qa-2 is associated with malignancy, epithelial-mesenchymal transition and stemness in breast cancer cells

Abstract Qa-2 is believed to mediate a protective immune response against cancer; however, little is known about the role of Qa-2 in tumorigenesis. Here, we used 4T1 breast cancer cells to study the involvement of Qa-2 in tumor progression in a syngeneic host. Qa-2 expression was reduced during in v...

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Autores principales:	Istéfani L. da Silva, Lucía Montero-Montero, Ester Martín-Villar, Jorge Martin-Pérez, Bruno Sainz, Jaime Renart, Renata Toscano Simões, Émerson Soares Veloso, Cláudia Salviano Teixeira, Mônica C. de Oliveira, Enio Ferreira, Miguel Quintanilla
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0210c082ddf440a2b7d396f89fb07501
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spelling	oai:doaj.org-article:0210c082ddf440a2b7d396f89fb075012021-12-02T12:32:00ZReduced expression of the murine HLA-G homolog Qa-2 is associated with malignancy, epithelial-mesenchymal transition and stemness in breast cancer cells10.1038/s41598-017-06528-x2045-2322https://doaj.org/article/0210c082ddf440a2b7d396f89fb075012017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06528-xhttps://doaj.org/toc/2045-2322Abstract Qa-2 is believed to mediate a protective immune response against cancer; however, little is known about the role of Qa-2 in tumorigenesis. Here, we used 4T1 breast cancer cells to study the involvement of Qa-2 in tumor progression in a syngeneic host. Qa-2 expression was reduced during in vivo tumor growth and in cell lines derived from 4T1-induced tumors. Tumor-derived cells elicited an epithelial-mesenchymal transition associated with upregulation of Zeb1 and Twist1/2 and enhanced tumor initiating and invasive capacities. Furthermore, these cells showed increased stem characteristics, as demonstrated by upregulation of Hes1, Sox2 and Oct3/4, and enrichment of CD44high/CD24median/low cells. Remarkably, Qa-2 cell-surface expression was excluded from the CD44high/CD24median/low subpopulation. Tumor-derived cells showed increased Src activity, and treatment of these cells with the Src kinase inhibitor PP2 enhanced Qa-2 but reduced Sox2 and CD44high/CD24median/low expression levels, suggesting that Src signaling, while positively associated with stemness, negatively regulates Qa-2 expression in breast cancer. Finally, overexpression of the Qa-2 family member Q7 on the cell surface slowed down in vivo tumor growth and reduced the metastatic potential of 4T1 cells. These results suggest an anti-malignant role for Qa-2 in breast cancer development, which appears to be absent from cancer stem cells.Istéfani L. da SilvaLucía Montero-MonteroEster Martín-VillarJorge Martin-PérezBruno SainzJaime RenartRenata Toscano SimõesÉmerson Soares VelosoCláudia Salviano TeixeiraMônica C. de OliveiraEnio FerreiraMiguel QuintanillaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Istéfani L. da Silva Lucía Montero-Montero Ester Martín-Villar Jorge Martin-Pérez Bruno Sainz Jaime Renart Renata Toscano Simões Émerson Soares Veloso Cláudia Salviano Teixeira Mônica C. de Oliveira Enio Ferreira Miguel Quintanilla Reduced expression of the murine HLA-G homolog Qa-2 is associated with malignancy, epithelial-mesenchymal transition and stemness in breast cancer cells
description	Abstract Qa-2 is believed to mediate a protective immune response against cancer; however, little is known about the role of Qa-2 in tumorigenesis. Here, we used 4T1 breast cancer cells to study the involvement of Qa-2 in tumor progression in a syngeneic host. Qa-2 expression was reduced during in vivo tumor growth and in cell lines derived from 4T1-induced tumors. Tumor-derived cells elicited an epithelial-mesenchymal transition associated with upregulation of Zeb1 and Twist1/2 and enhanced tumor initiating and invasive capacities. Furthermore, these cells showed increased stem characteristics, as demonstrated by upregulation of Hes1, Sox2 and Oct3/4, and enrichment of CD44high/CD24median/low cells. Remarkably, Qa-2 cell-surface expression was excluded from the CD44high/CD24median/low subpopulation. Tumor-derived cells showed increased Src activity, and treatment of these cells with the Src kinase inhibitor PP2 enhanced Qa-2 but reduced Sox2 and CD44high/CD24median/low expression levels, suggesting that Src signaling, while positively associated with stemness, negatively regulates Qa-2 expression in breast cancer. Finally, overexpression of the Qa-2 family member Q7 on the cell surface slowed down in vivo tumor growth and reduced the metastatic potential of 4T1 cells. These results suggest an anti-malignant role for Qa-2 in breast cancer development, which appears to be absent from cancer stem cells.
format	article
author	Istéfani L. da Silva Lucía Montero-Montero Ester Martín-Villar Jorge Martin-Pérez Bruno Sainz Jaime Renart Renata Toscano Simões Émerson Soares Veloso Cláudia Salviano Teixeira Mônica C. de Oliveira Enio Ferreira Miguel Quintanilla
author_facet	Istéfani L. da Silva Lucía Montero-Montero Ester Martín-Villar Jorge Martin-Pérez Bruno Sainz Jaime Renart Renata Toscano Simões Émerson Soares Veloso Cláudia Salviano Teixeira Mônica C. de Oliveira Enio Ferreira Miguel Quintanilla
author_sort	Istéfani L. da Silva
title	Reduced expression of the murine HLA-G homolog Qa-2 is associated with malignancy, epithelial-mesenchymal transition and stemness in breast cancer cells
title_short	Reduced expression of the murine HLA-G homolog Qa-2 is associated with malignancy, epithelial-mesenchymal transition and stemness in breast cancer cells
title_full	Reduced expression of the murine HLA-G homolog Qa-2 is associated with malignancy, epithelial-mesenchymal transition and stemness in breast cancer cells
title_fullStr	Reduced expression of the murine HLA-G homolog Qa-2 is associated with malignancy, epithelial-mesenchymal transition and stemness in breast cancer cells
title_full_unstemmed	Reduced expression of the murine HLA-G homolog Qa-2 is associated with malignancy, epithelial-mesenchymal transition and stemness in breast cancer cells
title_sort	reduced expression of the murine hla-g homolog qa-2 is associated with malignancy, epithelial-mesenchymal transition and stemness in breast cancer cells
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/0210c082ddf440a2b7d396f89fb07501
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Reduced expression of the murine HLA-G homolog Qa-2 is associated with malignancy, epithelial-mesenchymal transition and stemness in breast cancer cells

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