PMID- 34830485
OWN - NLM
STAT- MEDLINE
DCOM- 20211216
LR  - 20231213
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 22
IP  - 22
DP  - 2021 Nov 22
TI  - Connexin46 Expression Enhances Cancer Stem Cell and Epithelial-to-Mesenchymal 
      Transition Characteristics of Human Breast Cancer MCF-7 Cells.
LID - 10.3390/ijms222212604 [doi]
LID - 12604
AB  - 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.
FAU - Acuna, Rodrigo A
AU  - Acuna RA
AUID- ORCID: 0000-0002-2033-3107
AD  - Centro de Medicina Regenerativa, Facultad de Medicina, Clinica Alemana 
      Universidad del Desarrollo, Santiago 7780272, Chile.
FAU - Varas-Godoy, Manuel
AU  - Varas-Godoy M
AUID- ORCID: 0000-0001-5857-4793
AD  - Centro de Biologia Celular y Biomedicina (CEBICEM), Facultad de Medicina y 
      Ciencia, Universidad San Sebastian, Santiago 7510157, Chile.
FAU - Herrera-Sepulveda, Diego
AU  - Herrera-Sepulveda D
AD  - Carrera de Medicina Universidad del Desarrollo, Facultad de Medicina, Clinica 
      Alemana Universidad del Desarrollo, Santiago 7780272, Chile.
FAU - Retamal, Mauricio A
AU  - Retamal MA
AUID- ORCID: 0000-0003-2562-6686
AD  - Centro de Fisiologia Celular e Integrativa, Facultad de Medicina Clinica Alemana, 
      Universidad del Desarrollo, Santiago 7780272, Chile.
AD  - Programa de Comunicacion Celular en Cancer, Facultad de Medicina Clinica Alemana, 
      Universidad del Desarrollo, Santiago 7780272, Chile.
LA  - eng
GR  - 11200835/Fondo Nacional de Desarrollo Cientifico y Tecnologico/
GR  - 1160227/Fondo Nacional de Desarrollo Cientifico y Tecnologico/
GR  - 1190928/Fondo Nacional de Desarrollo Cientifico y Tecnologico/
PT  - Journal Article
DEP - 20211122
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Connexins)
RN  - 0 (Nanog Homeobox Protein)
RN  - 0 (SOX2 protein, human)
RN  - 0 (SOXB1 Transcription Factors)
RN  - 0 (VEGFA protein, human)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 0 (ZEB1 protein, human)
RN  - 0 (Zinc Finger E-box-Binding Homeobox 1)
RN  - 0 (GJA3 protein, human)
SB  - IM
MH  - Breast Neoplasms/*genetics/pathology
MH  - Cell Line, Tumor
MH  - Connexins/*genetics
MH  - Epithelial-Mesenchymal Transition/*genetics
MH  - Female
MH  - Gene Expression Regulation, Neoplastic/genetics
MH  - Human Umbilical Vein Endothelial Cells
MH  - Humans
MH  - MCF-7 Cells
MH  - Nanog Homeobox Protein/genetics
MH  - Neoplastic Stem Cells/*metabolism/pathology
MH  - SOXB1 Transcription Factors/genetics
MH  - Vascular Endothelial Growth Factor A/genetics
MH  - Zinc Finger E-box-Binding Homeobox 1/genetics
PMC - PMC8624448
OTO - NOTNLM
OT  - Connexin46
OT  - breast cancer
OT  - cancer stem cells
OT  - epithelial-to-mesenchymal transition
OT  - stemness
COIS- The authors declare no conflict of interest, financial or otherwise.
EDAT- 2021/11/28 06:00
MHDA- 2021/12/17 06:00
PMCR- 2021/11/22
CRDT- 2021/11/27 01:12
PHST- 2021/08/31 00:00 [received]
PHST- 2021/10/22 00:00 [revised]
PHST- 2021/11/03 00:00 [accepted]
PHST- 2021/11/27 01:12 [entrez]
PHST- 2021/11/28 06:00 [pubmed]
PHST- 2021/12/17 06:00 [medline]
PHST- 2021/11/22 00:00 [pmc-release]
AID - ijms222212604 [pii]
AID - ijms-22-12604 [pii]
AID - 10.3390/ijms222212604 [doi]
PST - epublish
SO  - Int J Mol Sci. 2021 Nov 22;22(22):12604. doi: 10.3390/ijms222212604.