title: Nerve growth factor and proNGF simultaneously promote symmetric self-renewal, quiescence, and epithelial to mesenchymal transition to enlarge the breast cancer stem cell compartment.
abstract: The discovery of cancer stem cells (CSCs) fundamentally advanced our understanding of the mechanisms governing breast cancer development. However, the stimuli that control breast CSC self-renewal and differentiation have still not been fully detailed. We previously showed that nerve growth factor (NGF) and its precursor proNGF can stimulate breast cancer cell growth and invasion in an autocrine manner. In this study, we investigated the effects of NGF and proNGF on the breast CSC compartment and found that NGF or proNGF enrich for CSCs in several breast cancer cell lines. This enrichment appeared to be achieved by increasing the number of symmetric divisions of quiescent/slow-proliferating CSCs. Interestingly, in vitro NGF pretreatment of MCF-7 luminal breast cancer cells promoted epithelial to mesenchymal transition in tumors of severe combined immunodeficient mice. Furthermore, p75(NTR), the common receptor for both neurotrophins and proneurotrophins, mediated breast CSC self-renewal by regulating the expression of pluripotency transcription factors. Our data indicate, for the first time, that the NGF/proNGF/p75(NTR) axis plays a critical role in regulating breast CSC self-renewal and plasticity.
authors.affiliation: Inserm U908, Villeneuve d'Ascq, France; Université Lille 1, Villeneuve d'Ascq, France; Inserm U837 Jean-Pierre Aubert Research Center, Institut pour la Recherche sur le Cancer de Lille (IRCL), Lille, France.
authors.forename: Elisa
authors.initials: E
authors.lastname: Tomellini
authors.forename: Yasmine
authors.initials: Y
authors.lastname: Touil
authors.forename: Chann
authors.initials: C
authors.lastname: Lagadec
authors.forename: Sylvain
authors.initials: S
authors.lastname: Julien
authors.forename: Pauline
authors.initials: P
authors.lastname: Ostyn
authors.forename: Nathalie
authors.initials: N
authors.lastname: Ziental-Gelus
authors.forename: Samuel
authors.initials: S
authors.lastname: Meignan
authors.forename: Justine
authors.initials: J
authors.lastname: Lengrand
authors.forename: Eric
authors.initials: E
authors.lastname: Adriaenssens
authors.forename: Renata
authors.initials: R
authors.lastname: Polakowska
authors.forename: Xuefen
authors.initials: X
authors.lastname: Le Bourhis
mesh_terms: D000818:Animals; D019898:Autocrine Communication; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000378:metabolism*; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D020932:Nerve Growth Factor / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism*; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism; D055153:Stem Cell Niche
chemical_list: C502240:NGF protein, human; C484065:NGFR protein, human; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D011498:Protein Precursors; D017475:Receptors, Nerve Growth Factor; C061397:pro-nerve growth factor, human; D020932:Nerve Growth Factor
keywords: Breast cancer stem cells; Nerve growth factor; p75NTR; proNGF