Beyond the channel: Role of connexins in regulating normal and cancerous processes in the mammary gland

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.