Nerve Growth Factor and proNGF Simultaneously Promote Symmetric Self-Renewal, Quiescence, and Epithelial to Mesenchymal Transition to Enlarge the Breast Cancer Stem Cell Compartment
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- Elisa Tomellini
- Inserm U908, Villeneuve d'Ascq, France
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- Yasmine Touil
- Inserm U837 Jean-Pierre Aubert Research Center, Institut pour la Recherche sur le Cancer de Lille (IRCL), Lille, France
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- Chann Lagadec
- Inserm U908, Villeneuve d'Ascq, France
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- Sylvain Julien
- Université Lille 1, Villeneuve d'Ascq, France
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- Pauline Ostyn
- Inserm U837 Jean-Pierre Aubert Research Center, Institut pour la Recherche sur le Cancer de Lille (IRCL), Lille, France
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- Nathalie Ziental-Gelus
- Inserm U908, Villeneuve d'Ascq, France
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- Samuel Meignan
- Inserm U908, Villeneuve d'Ascq, France
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- Justine Lengrand
- Inserm U908, Villeneuve d'Ascq, France
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- Eric Adriaenssens
- Université Lille 1, Villeneuve d'Ascq, France
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- Renata Polakowska
- Inserm U837 Jean-Pierre Aubert Research Center, Institut pour la Recherche sur le Cancer de Lille (IRCL), Lille, France
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- Xuefen Le Bourhis
- Inserm U908, Villeneuve d'Ascq, France
抄録
<jats:title>Abstract</jats:title> <jats:p>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, p75NTR, 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/p75NTR axis plays a critical role in regulating breast CSC self-renewal and plasticity. Stem Cells 2015;33:342–353</jats:p>
収録刊行物
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- Stem Cells
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Stem Cells 33 (2), 342-353, 2015-01-22
Oxford University Press (OUP)