Stem cells (SCs) within the mammary gland play a key role in driving mammary gland development, and their deregulation is thought to underlie the origin of certain types of breast cancer. However, the precise molecular identity of mammary SCs, and the factors that regulate their function, remain poorly defined. In this issue, Marie-Ange Deugnier and colleagues report a novel role for the transmembrane glycoprotein podoplanin (Pdpn) in controlling mammary SC function and tumorigenesis in mice. They demonstrate that Pdpn is expressed exclusively in the basal compartment of the postnatal mammary gland, including within multipotent basal SCs. The specific deletion of Pdpn in basal SCs gives rise to mammary gland branching defects in mice and restricts the developmental potential of basal SCs in vitro. The researchers further report that the expression of Wnt/β-Cat signaling pathway components is perturbed in Pdpn-null basal cells, and following on from this they demonstrate that Pdpn can potentiate Wnt/β-Cat signaling. Finally, they reveal that Pdpn loss can attenuate tumor formation in a mouse model of β-Cat-induced mammary tumorigenesis. Overall, this study uncovers an important role for Pdpn in mammary SC function and tumorigenesis, and also identifies Pdpn as a novel regulator of Wnt/β-Cat signaling.
