Autres actus

Comment la podoplanine régule la fonction des cellules souches mammaires et la tumorigenèse

redim-Pdpn- Curie copie

Une étude mené par l’équipe Mécanismes moléculaires du développement de la glande mammaire (Institut Curie/CNRS) dirigée par Marina Glukhova met au jour un rôle important de la podoplanine (Pdpn) dans le développement mammaire et la tumorigenèse, et l’identifie également comme un nouveau régulateur de la signalisation Wnt/βcat.

Stem cells (SCs) drive mammary development, giving rise postnatally to an epithelial bilayer composed of luminal and basal myoepithelial cells. Dysregulation of SCs is thought to be at the origin of certain breast cancers; however, the molecular identity of SCs and the factors regulating their function remain poorly defined. We identified the transmembrane protein podoplanin (Pdpn) as a specific marker of the basal compartment, including multipotent SCs, and found Pdpn localized at the basal-luminal interface. Embryonic deletion of Pdpn targeted to basal cells diminished basal and luminal SC activity and affected the expression of several Wnt/β-catenin signaling components in basal cells. Moreover, Pdpn loss attenuated mammary tumor formation in a mouse model of β-catenin-induced breast cancer, limiting tumor-initiating cell expansion and promoting molecular features associated with mesenchymal-to-epithelial cell transition. In line with the loss-of-function data, we demonstrated that mechanistically Pdpn enhances Wnt/β-catenin signaling in mammary basal cells. Overall, this study uncovers a role for Pdpn in mammary SC function and, importantly, identifies Pdpn as a new regulator of Wnt/β-catenin signaling, a key pathway in mammary development and tumorigenesis.

Podoplanin regulates mammary stem cell function and tumorigenesis by potentiating Wnt/β-catenin signaling
Bresson L, Faraldo MM, Di-Cicco A, Quintanilla M, Glukhova MA, Deugnier MA
Development 2018 145: dev160382