Connexin46 Expression Enhances Cancer Stem Cell and Epithelial-to-Mesenchymal Transition Characteristics of Human Breast Cancer MCF-7 Cells

Connexins (Cxs) are a family of proteins that form two different types of ion channels: hemichannels and gap junction channels. These channels participate in cellular communication, enabling them to share information and act as a synchronized syncytium. This cellular communication has been considere...

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Autores principales:	Rodrigo A. Acuña, Manuel Varas-Godoy, Diego Herrera-Sepulveda, Mauricio A. Retamal
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	Connexin46 breast cancer cancer stem cells epithelial-to-mesenchymal transition stemness Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/0fd24a24197f46de995d70c4cc63491c
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spelling	oai:doaj.org-article:0fd24a24197f46de995d70c4cc63491c2021-11-25T17:58:15ZConnexin46 Expression Enhances Cancer Stem Cell and Epithelial-to-Mesenchymal Transition Characteristics of Human Breast Cancer MCF-7 Cells10.3390/ijms2222126041422-00671661-6596https://doaj.org/article/0fd24a24197f46de995d70c4cc63491c2021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12604https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Connexins (Cxs) are a family of proteins that form two different types of ion channels: hemichannels and gap junction channels. These channels participate in cellular communication, enabling them to share information and act as a synchronized syncytium. This cellular communication has been considered a strong tumor suppressor, but it is now recognized that some type of Cxs can be pro-tumorigenic. For example, Cx46 expression is increased in human breast cancer samples and correlates with cancer stem cell (CSC) characteristics in human glioma. Thus, we explored whether Cx46 and glioma cells, can set up CSC and epithelial-to-mesenchymal transition (EMT) properties in a breast cancer cell line. To this end, we transfected MCF-7 cells with Cx46 attached to a green fluorescent protein (Cx46GFP), and we determined how its expression orchestrates both the gene-expression and functional changes associated with CSC and EMT. We observed that Cx46GFP increased Sox2, Nanog, and OCT4 mRNA levels associated with a high capacity to form monoclonal colonies and tumorspheres. Similarly, Cx46GFP increased the mRNA levels of n-cadherin, Vimentin, Snail and Zeb1 to a higher migratory and invasive capacity. Furthermore, Cx46GFP transfected in MCF-7 cells induced the release of higher amounts of VEGF, which promoted angiogenesis in HUVEC cells. We demonstrated for the first time that Cx46 modulates CSC and EMT properties in breast cancer cells and thus could be relevant in the design of future cancer therapies.Rodrigo A. AcuñaManuel Varas-GodoyDiego Herrera-SepulvedaMauricio A. RetamalMDPI AGarticleConnexin46breast cancercancer stem cellsepithelial-to-mesenchymal transitionstemnessBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12604, p 12604 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Connexin46 breast cancer cancer stem cells epithelial-to-mesenchymal transition stemness Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	Connexin46 breast cancer cancer stem cells epithelial-to-mesenchymal transition stemness Biology (General) QH301-705.5 Chemistry QD1-999 Rodrigo A. Acuña Manuel Varas-Godoy Diego Herrera-Sepulveda Mauricio A. Retamal Connexin46 Expression Enhances Cancer Stem Cell and Epithelial-to-Mesenchymal Transition Characteristics of Human Breast Cancer MCF-7 Cells
description	Connexins (Cxs) are a family of proteins that form two different types of ion channels: hemichannels and gap junction channels. These channels participate in cellular communication, enabling them to share information and act as a synchronized syncytium. This cellular communication has been considered a strong tumor suppressor, but it is now recognized that some type of Cxs can be pro-tumorigenic. For example, Cx46 expression is increased in human breast cancer samples and correlates with cancer stem cell (CSC) characteristics in human glioma. Thus, we explored whether Cx46 and glioma cells, can set up CSC and epithelial-to-mesenchymal transition (EMT) properties in a breast cancer cell line. To this end, we transfected MCF-7 cells with Cx46 attached to a green fluorescent protein (Cx46GFP), and we determined how its expression orchestrates both the gene-expression and functional changes associated with CSC and EMT. We observed that Cx46GFP increased Sox2, Nanog, and OCT4 mRNA levels associated with a high capacity to form monoclonal colonies and tumorspheres. Similarly, Cx46GFP increased the mRNA levels of n-cadherin, Vimentin, Snail and Zeb1 to a higher migratory and invasive capacity. Furthermore, Cx46GFP transfected in MCF-7 cells induced the release of higher amounts of VEGF, which promoted angiogenesis in HUVEC cells. We demonstrated for the first time that Cx46 modulates CSC and EMT properties in breast cancer cells and thus could be relevant in the design of future cancer therapies.
format	article
author	Rodrigo A. Acuña Manuel Varas-Godoy Diego Herrera-Sepulveda Mauricio A. Retamal
author_facet	Rodrigo A. Acuña Manuel Varas-Godoy Diego Herrera-Sepulveda Mauricio A. Retamal
author_sort	Rodrigo A. Acuña
title	Connexin46 Expression Enhances Cancer Stem Cell and Epithelial-to-Mesenchymal Transition Characteristics of Human Breast Cancer MCF-7 Cells
title_short	Connexin46 Expression Enhances Cancer Stem Cell and Epithelial-to-Mesenchymal Transition Characteristics of Human Breast Cancer MCF-7 Cells
title_full	Connexin46 Expression Enhances Cancer Stem Cell and Epithelial-to-Mesenchymal Transition Characteristics of Human Breast Cancer MCF-7 Cells
title_fullStr	Connexin46 Expression Enhances Cancer Stem Cell and Epithelial-to-Mesenchymal Transition Characteristics of Human Breast Cancer MCF-7 Cells
title_full_unstemmed	Connexin46 Expression Enhances Cancer Stem Cell and Epithelial-to-Mesenchymal Transition Characteristics of Human Breast Cancer MCF-7 Cells
title_sort	connexin46 expression enhances cancer stem cell and epithelial-to-mesenchymal transition characteristics of human breast cancer mcf-7 cells
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/0fd24a24197f46de995d70c4cc63491c
work_keys_str_mv	AT rodrigoaacuna connexin46expressionenhancescancerstemcellandepithelialtomesenchymaltransitioncharacteristicsofhumanbreastcancermcf7cells AT manuelvarasgodoy connexin46expressionenhancescancerstemcellandepithelialtomesenchymaltransitioncharacteristicsofhumanbreastcancermcf7cells AT diegoherrerasepulveda connexin46expressionenhancescancerstemcellandepithelialtomesenchymaltransitioncharacteristicsofhumanbreastcancermcf7cells AT mauricioaretamal connexin46expressionenhancescancerstemcellandepithelialtomesenchymaltransitioncharacteristicsofhumanbreastcancermcf7cells
_version_	1718411785801826304

Connexin46 Expression Enhances Cancer Stem Cell and Epithelial-to-Mesenchymal Transition Characteristics of Human Breast Cancer MCF-7 Cells

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