title: Paracrine Met signaling triggers epithelial-mesenchymal transition in mammary luminal progenitors, affecting their fate.
abstract: 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.
authors.affiliation: Institut Curie, Paris Sciences et Lettres Research University, Paris, France.
authors.forename: Amandine
authors.initials: A
authors.lastname: Di-Cicco
authors.affiliation: Institut Curie, Paris Sciences et Lettres Research University, Paris, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Petit
authors.affiliation: Institut Curie, Paris Sciences et Lettres Research University, Paris, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Chiche
authors.affiliation: Institut Curie, Paris Sciences et Lettres Research University, Paris, France.
authors.forename: Laura
authors.initials: L
authors.lastname: Bresson
authors.affiliation: Institut Curie, Paris Sciences et Lettres Research University, Paris, France.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Romagnoli
authors.affiliation: Karlsruhe Institute of Technology, Karlsruhe, Germany.
authors.forename: Véronique
authors.initials: V
authors.lastname: Orian-Rousseau
authors.affiliation: Cell Biology and Stem Cells Unit, CIC bioGUNE, Derio, Spain.
authors.forename: Maria dM
authors.initials: Md
authors.lastname: Vivanco
authors.affiliation: Baylor College of Medicine, Houston, United States.
authors.forename: Daniel
authors.initials: D
authors.lastname: Medina
authors.affiliation: Institut Curie, Paris Sciences et Lettres Research University, Paris, France.
authors.forename: Marisa M
authors.initials: MM
authors.lastname: Faraldo
authors.affiliation: Institut Curie, Paris Sciences et Lettres Research University, Paris, France.
authors.forename: Marina A
authors.initials: MA
authors.lastname: Glukhova
authors.affiliation: Institut Curie, Paris Sciences et Lettres Research University, Paris, France.
authors.forename: Marie-Ange
authors.initials: MA
authors.lastname: Deugnier
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000187:drug effects / Q000502:physiology; D058750:Epithelial-Mesenchymal Transition; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D051379:Mice; D019899:Paracrine Communication; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D015398:Signal Transduction; D013234:Stem Cells / Q000187:drug effects / Q000502:physiology*
chemical_list: C553307:HGF protein, mouse; D017228:Hepatocyte Growth Factor; C000606763:HGFR protein, mouse; D019859:Proto-Oncogene Proteins c-met
keywords: ICAM-1; Met signaling; developmental biology; epithelial–mesenchymal transition; mammary gland; mouse; stem cells