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Gap Junctions and Wnt Signaling in the Mammary Gland: a Cross-Talk?

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Journal of Mammary Gland Biology and Neoplasia Aims and scope Submit manuscript

Abstract

Connexins (Cxs), the building blocks of gap junctions (GJs), exhibit spatiotemporal patterns of expression and regulate the development and differentiation of the mammary gland, acting via channel-dependent and channel-independent mechanisms. Impaired Cx expression and localization are reported in breast cancer, suggesting a tumor suppressive role for Cxs. The signaling events that mediate the role of GJs in the development and tumorigenesis of the mammary gland remain poorly identified. The Wnt pathways, encompassing the canonical or the Wnt/β-catenin pathway and the noncanonical β-catenin-independent pathway, also play important roles in those processes. Indeed, aberrant Wnt signaling is associated with breast cancer. Despite the coincident roles of Cxs and Wnt pathways, the cross-talk in the breast tissue is poorly defined, although this is reported in a number of other tissues. Our previous studies revealed a channel-independent role for Cx43 in inducing differentiation or suppressing tumorigenesis of mammary epithelial cells by acting as a negative regulator of the Wnt/β-catenin pathway. Here, we provide a brief overview of mammary gland development, with emphasis on the role of Cxs in development and tumorigenesis of this tissue. We also discuss the role of Wnt signaling in similar contexts, and review the literature illustrating interplay between Cxs and Wnt pathways.

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Abbreviations

GJ:

Gap junction

Cx:

Connexin

GJIC:

Gap junctional intercellular communication

TEB:

Terminal end bud

TDLU:

Terminal duct lobular unit

ECM:

Extracellular matrix

3-D:

3-Dimensional

3'-UTR:

3'-Untranslated region

STAT5:

Signal transducer and activator of transcription 5

VEGF:

Vascular endothelial growth factor

TSP-1:

Thrombospondin 1

PCP:

Planar cell polarity

APC:

Adenomatous polyposis coli

CK1:

Casein kinase 1

GSK-3:

Glycogen synthase kinase 3

TCF:

T-cell factor

LEF:

Lymphoid enhancer factor

Gro:

Groucho

TLE:

Transducin-like enhancer

HDAC:

Histone deacetylase

Fzd:

Frizzled

LRP5/6:

Low-density lipoprotein receptor-related protein 5 or 6

Dvl:

Dishevelled

CDK1:

Cyclin-dependent kinase 1

DKK1:

Dikkopf 1

sFRP:

Secreted frizzled-related protein

WIF1:

Wnt inhibitory factor 1

Panx3:

Pannexin 3

Rb:

Retinoblastoma

GSC:

Glioma stem cell

GFAP:

Glial fibrillary acidic protein

MSC:

Mesenchymal stem cell

Rho:

Ras homolog

JNK:

c-Jun N-terminal kinase

Daam1:

Dishevelled-associated activator of morphogenesis 1

GEF:

Guanine nucleotide exchange factor

ROCK:

Rho-associated kinase

ER:

Endoplasmic reticulum

PKC:

Protein kinase C

CaMKII:

Calcium/calmodulin-dependent protein kinase II

NFAT:

Nuclear factor of activated T-cells

PAK1:

p21-activated kinase 1

FRET:

Forster resonance energy transfer

EGF:

Epidermal growth factor

MMP:

Matrix metalloproteinase

MLC:

Myosin light chain

TJ:

Tight junction

AJ:

Adherens junction

MDCK:

Madin-Darby canine kidney

MTOC:

Microtubule-organizing center

GDI:

Guanine nucleotide dissociation inhibitor

α-MHC:

α-Myosin heavy chain

BCR:

B-cell receptor

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Acknowledgements

This work was supported by a grant from the Lebanese National Council for Scientific Research (CNRS-L) and the AUB University Research Board (URB) to Rabih S. Talhouk, and the LAU School of Arts and Science Research and Development Council (SAS-RDC) to Mirvat El-Sibai.

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  1. Department of Biology, Faculty of Arts and Sciences, American University of Beirut (AUB), P.O. Box: 11-0236, Beirut, Lebanon

    Sabreen F. Fostok & Rabih S. Talhouk

  2. Department of Natural Sciences, School of Arts and Sciences, Lebanese American University (LAU), Beirut, Lebanon

    Mirvat El-Sibai

  3. Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut (AUB), Beirut, Lebanon

    Marwan El-Sabban

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  1. Sabreen F. Fostok
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Fostok, S.F., El-Sibai, M., El-Sabban, M. et al. Gap Junctions and Wnt Signaling in the Mammary Gland: a Cross-Talk?. J Mammary Gland Biol Neoplasia 24, 17–38 (2019). https://doi.org/10.1007/s10911-018-9411-5

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  • DOI: https://doi.org/10.1007/s10911-018-9411-5

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