| First Author | Desgrosellier JS | Year | 2014 |
| Journal | Dev Cell | Volume | 30 |
| Issue | 3 | Pages | 295-308 |
| PubMed ID | 25117682 | Mgi Jnum | J:214219 |
| Mgi Id | MGI:5588591 | Doi | 10.1016/j.devcel.2014.06.005 |
| Citation | Desgrosellier JS, et al. (2014) Integrin alphavbeta3 drives slug activation and stemness in the pregnant and neoplastic mammary gland. Dev Cell 30(3):295-308 |
| abstractText | Although integrin alphavbeta3 is linked to cancer progression, its role in epithelial development is unclear. Here, we show that alphavbeta3 plays a critical role in adult mammary stem cells (MaSCs) during pregnancy. Whereas alphavbeta3 is a luminal progenitor marker in the virgin gland, we noted increased alphavbeta3 expression in MaSCs at midpregnancy. Accordingly, mice lacking alphavbeta3 or expressing a signaling-deficient receptor showed defective mammary gland morphogenesis during pregnancy. This was associated with decreased MaSC expansion, clonogenicity, and expression of Slug, a master regulator of MaSCs. Surprisingly, alphavbeta3-deficient mice displayed normal development of the virgin gland with no effect on luminal progenitors. Transforming growth factor beta2 (TGF-beta2) induced alphavbeta3 expression, enhancing Slug nuclear accumulation and MaSC clonogenicity. In human breast cancer cells, alphavbeta3 was necessary and sufficient for Slug activation, tumorsphere formation, and tumor initiation. Thus, pregnancy-associated MaSCs require a TGF-beta2/alphavbeta3/Slug pathway, which may contribute to breast cancer progression and stemness. |
