Connexins: a junctional crossroad to breast cancer

The mammary gland presents a valuable model for developmental studies, spanning the embryonic stage through menarche to menopause. The dynamic remodeling of this gland is orchestrated by cellular heterogeneity, integrating mammogenic, systemic and local cues. Gap junctional intercellular communication provides pivotal cross talk of mammary epithelial cells with the surrounding cells and their local microenvironment. Connexins are involved in regulating normal and pathological mammary gland development, through channel-dependent and channel-independent roles. Modulation of the isoforms of connexins expressed, as well as their differential assembly into connexons and recruitment of a variety of associated partners, contributes to the complexity of signaling relayed at the membrane. This confers context-dependent functions of connexins at different stages of development and carcinogenesis. This review will summarize available knowledge about the functional dynamics of connexins and gap junctions in regulating normal mammary gland development and its pathophysiology.