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

International Journal of Molecular Sciences
Mélanie BusbyIsabelle Plante

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 ...Continue Reading

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Citations

Mar 7, 2019·The American Journal of Dermatopathology·Angel Fernandez-FloresEduardo Fonseca
Sep 6, 2020·Journal of Cellular and Molecular Medicine·Xiaofei QuWeijian Guo
May 13, 2020·Cancer Metastasis Reviews·Alejandra I FerrerPranela Rameshwar
Mar 1, 2019·Oncogene·Trond AasenArantxa Tabernero
Jan 1, 2021·Cancers·Chang-Xu ChenJean X Jiang
Apr 20, 2021·Nucleic Acids Research·Charbel AlfeghalySylvain Maenner
Aug 20, 2021·Proceedings of the National Academy of Sciences of the United States of America·David BuechelGerhard Christofori

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Methods Mentioned

BETA
transmission electron microscopy
chromosomal aberrations
protein assay

Software Mentioned

cBioportal
Bioconductor package
genefu
ROCR
KMPlotter
BreastMark
R
GISTIC
Limma
R genefu package

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