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

Wei Liu1, Ting Wu1, Xiaobing Dong1

  • 1State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, 200031, China.

Scientific Reports
|September 10, 2017
PubMed

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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