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Int. J. Mol. Sci. 2018, 19(3), 693; https://doi.org/10.3390/ijms19030693

The Complex Subtype-Dependent Role of Connexin 43 (GJA1) in Breast Cancer

1
INRS-Institut Armand-Frappier, Laval, QC H7V 1B7, Canada
2
Centre for Structural and Functional Genomics, Department of Biology, Concordia University, Montreal, QC H4B 1R6, Canada
*
Author to whom correspondence should be addressed.
Received: 31 January 2018 / Revised: 17 February 2018 / Accepted: 26 February 2018 / Published: 28 February 2018
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Abstract

Gap junction transmembrane channels allow the transfer of small molecules between the cytoplasm of adjacent cells. They are formed by proteins named connexins (Cxs) that have long been considered as a tumor suppressor. This widespread view has been challenged by recent studies suggesting that the role of Connexin 43 (Cx43) in cancer is tissue- and stage-specific and can even promote tumor progression. High throughput profiling of invasive breast cancer has allowed for the construction of subtyping schemes that partition patients into at least four distinct intrinsic subtypes. This study characterizes Cx43 expression during cancer progression with each of the tumor subtypes using a compendium of publicly available gene expression data. In particular, we show that Cx43 expression depends greatly on intrinsic subtype. Tumor grade also co-varies with patient subtype, resulting in Cx43 co-expression with grade in a subtype-dependent manner. Better survival was associated with a high expression of Cx43 in unstratified and luminal tumors but with a low expression in Her2e subtype. A better understanding of Cx43 regulation in a subtype-dependent manner is needed to clarify the context in which Cx43 is associated with tumor suppression or cancer progression. View Full-Text
Keywords: gap junctions; Connexin 43 (Cx43); breast cancer; survival analysis; intrinsic subtype gap junctions; Connexin 43 (Cx43); breast cancer; survival analysis; intrinsic subtype
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Busby, M.; Hallett, M.T.; Plante, I. The Complex Subtype-Dependent Role of Connexin 43 (GJA1) in Breast Cancer. Int. J. Mol. Sci. 2018, 19, 693.

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