Wnt and mammary stem cells: hormones cannot fly wingless

The mammary stem cell and its local microenvironment are central for the maintenance of proper tissue homeostasis during normal development. Defining the hierarchical organization of the epithelial subtypes in the mammary gland and the molecular pathways guiding their development has begun to provide a framework for understanding how cancer stem cells sustain the progression and heterogeneity of breast cancers. The Wnt pathway plays a fundamental role in multiple adult stem cells, as well as in orchestrating proper mammary gland development and maintenance. These processes are intricately guided by the influence of systemic hormones and local factors. Alterations in Wnt signaling can skew the homeostatic balance of the mammary epithelium to drive malignant progression; however, complexities of Wnt pathway components present a challenge in understanding their physiological function.