Affordable Access

deepdyve-link
Publisher Website

Podoplanin regulates mammary stem cell function and tumorigenesis by potentiating Wnt/β-catenin signaling.

Authors
  • Bresson, Laura1, 2, 3
  • Faraldo, Marisa M1, 4
  • Di-Cicco, Amandine1
  • Quintanilla, Miguel5
  • Glukhova, Marina A1, 4
  • Deugnier, Marie-Ange6, 4
  • 1 Institut Curie, PSL Research University, CNRS, UMR144, Paris, F-75248, France. , (France)
  • 2 Université Paris Sud, Université Paris-Saclay, F-91405, Orsay, France. , (France)
  • 3 Sorbonne Universités, UPMC Univ Paris 06, F-75005, Paris, France. , (France)
  • 4 INSERM, Paris, F-75013, France. , (France)
  • 5 Instituto de Investigaciones Biomedicas Alberto Sols, CSIC-UAM, Madrid, Spain. , (Spain)
  • 6 Institut Curie, PSL Research University, CNRS, UMR144, Paris, F-75248, France [email protected] , (France)
Type
Published Article
Journal
Development
Publisher
The Company of Biologists
Publication Date
Feb 21, 2018
Volume
145
Issue
4
Identifiers
DOI: 10.1242/dev.160382
PMID: 29361573
Source
Medline
Keywords
License
Unknown

Abstract

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.

Report this publication

Statistics

Seen <100 times