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Beyond the Channel: Role of Connexins in Regulating Normal and Cancerous Processes in the Mammary Gland

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Intercellular Communication in Cancer

Abstract

The mammary epithelium possesses a well-defined architecture mediated by cell-extracellular matrix and cell-cell junctions that is essential for the coordinated continuous development of the mammary gland. The dynamic remodeling of the mammary gland is orchestrated by cellular responses to environmental cues that are relayed through the interplay between cell-cell junctions themselves including tight junctions, adherens junctions, desmosomes and gap junctions, and their interacting partners, notably polarity proteins. In this chapter, we address the molecular dynamics of gap junctions and the roles that these junctions have been ascribed in modulating normal and mammary cancer behaviors. We aim to highlight how connexins, the building blocks of gap junctions, have transcended their gap junction-dependent functions as structural cellular components and are now perceived as signaling hubs. These structural entities are able to integrate messages from the cell’s surrounding and modulate cytoplasmic downstream signaling pathways that regulate cell function and often gene expression during the normal differentiation of the mammary epithelium. We also elaborate on the changes in the expression, function and localization of gap junctions and connexins and their consequences for mammary cancer progression. Finally, we present recent breast cancer therapies that target gap junction proteins.

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Acknowledgments

The authors are grateful to Sabreen Fostok for critical reading of the manuscript and to Diala El-Zein for working on the schematic diagrams. We wish to acknowledge the support of the American University of Beirut Research Board, the Lebanese National Council for Scientific Research (to RT and DB); and the UNESCO-L’ORÉAL International Fellowship for Women in Science-2012 (to DB). SL and RT are members of International Breast Cancer & Nutrition (IBCN).

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Authors and Affiliations

  1. Department of Biology, Faculty of Arts and Sciences, American University of Beirut (AUB), Beirut, Lebanon

    Dana Bazzoun & Rabih Talhouk

  2. Department of Basic Medical Sciences, Purdue University, West Lafayette, IN, USA

    Sophie Lelièvre

  3. Center for Cancer Research, Purdue University, West Lafayette, IN, USA

    Sophie Lelièvre

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  1. Dana Bazzoun
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  2. Sophie Lelièvre
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  3. Rabih Talhouk
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Correspondence to Rabih Talhouk .

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  1. Department of Pathology, Wayne State University School of Medicine, Detroit, Michigan, USA

    Mustapha Kandouz

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Bazzoun, D., Lelièvre, S., Talhouk, R. (2015). Beyond the Channel: Role of Connexins in Regulating Normal and Cancerous Processes in the Mammary Gland. In: Kandouz, M. (eds) Intercellular Communication in Cancer. Springer, Dordrecht. https://doi.org/10.1007/978-94-017-7380-5_1

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