Paracrine Met signaling triggers epithelial–mesenchymal transition in mammary luminal progenitors, affecting their fate
Amandine Di-Cicco,
Valérie Petit,
Aurélie Chiche,
Laura Bresson,
Mathilde Romagnoli,
Véronique Orian-Rousseau,
Maria dM Vivanco,
Daniel Medina,
Marisa M Faraldo,
Marina A Glukhova,
Marie-Ange Deugnier
Affiliations
Amandine Di-Cicco
Institut Curie, Paris Sciences et Lettres Research University, Paris, France; CNRS UMR144, Subcellular Structure and Cellular Dynamics - Institut Curie, Paris, France; Equipe Labellisée par La Ligue contre le Cancer, Paris, France
Valérie Petit
Institut Curie, Paris Sciences et Lettres Research University, Paris, France; CNRS UMR144, Subcellular Structure and Cellular Dynamics - Institut Curie, Paris, France
Aurélie Chiche
Institut Curie, Paris Sciences et Lettres Research University, Paris, France; CNRS UMR144, Subcellular Structure and Cellular Dynamics - Institut Curie, Paris, France; Equipe Labellisée par La Ligue contre le Cancer, Paris, France
Laura Bresson
Institut Curie, Paris Sciences et Lettres Research University, Paris, France; CNRS UMR144, Subcellular Structure and Cellular Dynamics - Institut Curie, Paris, France; Equipe Labellisée par La Ligue contre le Cancer, Paris, France
Mathilde Romagnoli
Institut Curie, Paris Sciences et Lettres Research University, Paris, France; CNRS UMR144, Subcellular Structure and Cellular Dynamics - Institut Curie, Paris, France; Equipe Labellisée par La Ligue contre le Cancer, Paris, France
Véronique Orian-Rousseau
Karlsruhe Institute of Technology, Karlsruhe, Germany
Maria dM Vivanco
Cell Biology and Stem Cells Unit, CIC bioGUNE, Derio, Spain
Daniel Medina
Baylor College of Medicine, Houston, United States
Marisa M Faraldo
Institut Curie, Paris Sciences et Lettres Research University, Paris, France; CNRS UMR144, Subcellular Structure and Cellular Dynamics - Institut Curie, Paris, France; Equipe Labellisée par La Ligue contre le Cancer, Paris, France; Institut national de la santé et de la recherche médicale, Paris, France
Marina A Glukhova
Institut Curie, Paris Sciences et Lettres Research University, Paris, France; CNRS UMR144, Subcellular Structure and Cellular Dynamics - Institut Curie, Paris, France; Equipe Labellisée par La Ligue contre le Cancer, Paris, France; Institut national de la santé et de la recherche médicale, Paris, France
Marie-Ange Deugnier
Institut Curie, Paris Sciences et Lettres Research University, Paris, France; CNRS UMR144, Subcellular Structure and Cellular Dynamics - Institut Curie, Paris, France; Equipe Labellisée par La Ligue contre le Cancer, Paris, France; Institut national de la santé et de la recherche médicale, Paris, France
HGF/Met signaling has recently been associated with basal-type breast cancers, which are thought to originate from progenitor cells residing in the luminal compartment of the mammary epithelium. We found that ICAM-1 efficiently marks mammary luminal progenitors comprising hormone receptor-positive and receptor-negative cells, presumably ductal and alveolar progenitors. Both cell populations strongly express Met, while HGF is produced by stromal and basal myoepithelial cells. We show that persistent HGF treatment stimulates the clonogenic activity of ICAM1-positive luminal progenitors, controlling their survival and proliferation, and leads to the expression of basal cell characteristics, including stem cell potential. This is accompanied by the induction of Snai1 and Snai2, two major transcription factors triggering epithelial–mesenchymal transition, the repression of the luminal-regulatory genes Elf5 and Hey1, and claudin down-regulation. Our data strongly indicate that paracrine Met signaling can control the function of luminal progenitors and modulate their fate during mammary development and tumorigenesis.
