| First Author | Joshi PA | Year | 2015 |
| Journal | Stem Cell Reports | Volume | 5 |
| Issue | 1 | Pages | 31-44 |
| PubMed ID | 26095608 | Mgi Jnum | J:345731 |
| Mgi Id | MGI:6837938 | Doi | 10.1016/j.stemcr.2015.05.012 |
| Citation | Joshi PA, et al. (2015) RANK Signaling Amplifies WNT-Responsive Mammary Progenitors through R-SPONDIN1. Stem Cell Reports 5(1):31-44 |
| abstractText | Systemic and local signals must be integrated by mammary stem and progenitor cells to regulate their cyclic growth and turnover in the adult gland. Here, we show RANK-positive luminal progenitors exhibiting WNT pathway activation are selectively expanded in the human breast during the progesterone-high menstrual phase. To investigate underlying mechanisms, we examined mouse models and found that loss of RANK prevents the proliferation of hormone receptor-negative luminal mammary progenitors and basal cells, an accompanying loss of WNT activation, and, hence, a suppression of lobuloalveologenesis. We also show that R-spondin1 is depleted in RANK-null progenitors, and that its exogenous administration rescues key aspects of RANK deficiency by reinstating a WNT response and mammary cell expansion. Our findings point to a novel role of RANK in dictating WNT responsiveness to mediate hormone-induced changes in the growth dynamics of adult mammary cells. |
