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 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.

Cite this document

Acuña, R. A., Varas-Godoy, M., Herrera-Sepulveda, D., & Retamal, M. A. (2021). Connexin46 expression enhances cancer stem cell and epithelial-to-mesenchymal transition characteristics of human breast cancer mcf-7 cells. International Journal of Molecular Sciences, 22(22), 12604. https://doi.org/10.3390/ijms222212604

Project(s)

Extracellular vesicles derived from Connexin 46-breast cancer cells promote malignancy through the transfer of metastasis-associated miRNAs mediated by Connexin channel activity

Carbon monoxide inhibits Cx46 HCs through a lipid peroxidation-dependent process which increases Cx46- Ca2+ sensitivity

Subjects

connexin46

;

breast cancer

;

cancer stem cells

;

epithelial-to-mesenchymal transition

;

stemness

;

breast neoplasms

;

cell line, tumor

;

connexins

;

epithelial-mesenchymal transition

;

female

;

gene expression regulation, neoplastic

;

human umbilical vein endothelial cells

;

humans

;

mcf-7 cells

;

nanog homeobox protein

;

neoplastic stem cells

;

soxb1 transcription factors

;

vascular endothelial growth factor a

;

zinc finger e-box-binding homeobox 1

;

connexin 46

;

green fluorescent protein

;

messenger rna

;

monoclonal antibody

;

nerve cell adhesion molecule

;

octamer transcription factor 4

;

transcription factor nanog

;

transcription factor snail

;

transcription factor sox2

;

transcription factor zeb1

;

vasculotropin

;

vimentin

;

connexin 46

;

gap junction protein

;

sox2 protein, human

;

transcription factor sox

;

vasculotropin a

;

vegfa protein, human

;

zeb1 protein, human

;

angiogenesis

;

article

;

cancer stem cell

;

cell migration

;

controlled study

;

epithelial mesenchymal transition

;

gene expression

;

genetic transfection

;

human

;

human cell

;

human tissue

;

huvec cell line

;

in vitro study

;

mcf-7 cell line

;

nonhuman

;

protein expression

;

protein secretion

;

tumor invasion

;

tumor spheroid

;

breast tumor

;

cancer stem cell

;

epithelial mesenchymal transition

;

female

;

gene expression regulation

;

genetics

;

mcf-7 cell line

;

metabolism

;

pathology

;

tumor cell line

;

umbilical vein endothelial cell