Neuropilin-1 is upregulated by Wnt/β-catenin signaling and is important for mammary stem cells

Wnt/β-catenin signaling is instrumental for the development of mammary gland and the properties of mammary stem cells (MaSCs). The Wnt signaling downstream effectors that engage in regulating MaSCs have not been extensively studied. Here, we report that Neuropilin-1 (Nrp1) expression is induced by W...

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Autores principales: Liu, Wei, Wu, Ting, Dong, Xiaobing, Zeng, Yi Arial
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5591238/
https://www.ncbi.nlm.nih.gov/pubmed/28887477
http://dx.doi.org/10.1038/s41598-017-11287-w
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author Liu, Wei
Wu, Ting
Dong, Xiaobing
Zeng, Yi Arial
author_facet Liu, Wei
Wu, Ting
Dong, Xiaobing
Zeng, Yi Arial
author_sort Liu, Wei
collection PubMed
description Wnt/β-catenin signaling is instrumental for the development of mammary gland and the properties of mammary stem cells (MaSCs). The Wnt signaling downstream effectors that engage in regulating MaSCs have not been extensively studied. Here, we report that Neuropilin-1 (Nrp1) expression is induced by Wnt/β-catenin signaling in MaSCs, and its function is critical for the activity of MaSCs. Nrp1 is particularly expressed in MaSCs that are marked by the expression of Protein C Receptor (Procr). Knockdown of Nrp1 by shRNA diminishes MaSCs’ in vitro colony formation and in vivo mammary gland reconstitution ability. Similar results are seen when antagonizing Nrp1 using a dominant negative peptide. In genetic experiments, deletion of Nrp1 results in delay of mammary development. In addition, knockdown of Nrp1 inhibits MMTV-Wnt1 tumor growth in xenograft. Our data demonstrate that Nrp1 is critical for mammary development and tumorigenesis, revealing new insights into MaSC regulation and targeting stem cells in treatment of breast cancer.
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spelling pubmed-55912382017-09-13 Neuropilin-1 is upregulated by Wnt/β-catenin signaling and is important for mammary stem cells Liu, Wei Wu, Ting Dong, Xiaobing Zeng, Yi Arial Sci Rep Article Wnt/β-catenin signaling is instrumental for the development of mammary gland and the properties of mammary stem cells (MaSCs). The Wnt signaling downstream effectors that engage in regulating MaSCs have not been extensively studied. Here, we report that Neuropilin-1 (Nrp1) expression is induced by Wnt/β-catenin signaling in MaSCs, and its function is critical for the activity of MaSCs. Nrp1 is particularly expressed in MaSCs that are marked by the expression of Protein C Receptor (Procr). Knockdown of Nrp1 by shRNA diminishes MaSCs’ in vitro colony formation and in vivo mammary gland reconstitution ability. Similar results are seen when antagonizing Nrp1 using a dominant negative peptide. In genetic experiments, deletion of Nrp1 results in delay of mammary development. In addition, knockdown of Nrp1 inhibits MMTV-Wnt1 tumor growth in xenograft. Our data demonstrate that Nrp1 is critical for mammary development and tumorigenesis, revealing new insights into MaSC regulation and targeting stem cells in treatment of breast cancer. Nature Publishing Group UK 2017-09-08 /pmc/articles/PMC5591238/ /pubmed/28887477 http://dx.doi.org/10.1038/s41598-017-11287-w Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Liu, Wei
Wu, Ting
Dong, Xiaobing
Zeng, Yi Arial
Neuropilin-1 is upregulated by Wnt/β-catenin signaling and is important for mammary stem cells
title Neuropilin-1 is upregulated by Wnt/β-catenin signaling and is important for mammary stem cells
title_full Neuropilin-1 is upregulated by Wnt/β-catenin signaling and is important for mammary stem cells
title_fullStr Neuropilin-1 is upregulated by Wnt/β-catenin signaling and is important for mammary stem cells
title_full_unstemmed Neuropilin-1 is upregulated by Wnt/β-catenin signaling and is important for mammary stem cells
title_short Neuropilin-1 is upregulated by Wnt/β-catenin signaling and is important for mammary stem cells
title_sort neuropilin-1 is upregulated by wnt/β-catenin signaling and is important for mammary stem cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5591238/
https://www.ncbi.nlm.nih.gov/pubmed/28887477
http://dx.doi.org/10.1038/s41598-017-11287-w
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