State 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.
Sci Rep. 2017 Sep 8;7(1):10941. doi: 10.1038/s41598-017-11287-w.
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.
Wnt/β-catenin 信号通路对于乳腺的发育和乳腺干细胞（MaSCs）的特性至关重要。目前，尚未对参与调节 MaSCs 的 Wnt 信号下游效应物进行广泛研究。本研究报告称，Neuropilin-1（Nrp1）在 MaSCs 中由 Wnt/β-catenin 信号诱导表达，其功能对于 MaSCs 的活性至关重要。Nrp1 特别在由 Protein C Receptor（Procr）表达标记的 MaSCs 中表达。通过 shRNA 敲低 Nrp1 会降低 MaSCs 在体外集落形成和体内乳腺重建能力。使用显性负性肽拮抗 Nrp1 时会产生类似的结果。在遗传实验中，Nrp1 的缺失导致乳腺发育延迟。此外，敲低 Nrp1 会抑制 MMTV-Wnt1 肿瘤在异种移植中的生长。本研究数据表明，Nrp1 对于乳腺发育和肿瘤发生至关重要，为 MaSC 调节和靶向乳腺癌治疗中的干细胞提供了新的见解。
