| First Author | Celià-Terrassa T | Year | 2017 |
| Journal | Nat Cell Biol | Volume | 19 |
| Issue | 6 | Pages | 711-723 |
| PubMed ID | 28530657 | Mgi Jnum | J:246199 |
| Mgi Id | MGI:5920866 | Doi | 10.1038/ncb3533 |
| Citation | Celia-Terrassa T, et al. (2017) Normal and cancerous mammary stem cells evade interferon-induced constraint through the miR-199a-LCOR axis. Nat Cell Biol 19(6):711-723 |
| abstractText | Tumour-initiating cells, or cancer stem cells (CSCs), possess stem-cell-like properties observed in normal adult tissue stem cells. Normal and cancerous stem cells may therefore share regulatory mechanisms for maintaining self-renewing capacity and resisting differentiation elicited by cell-intrinsic or microenvironmental cues. Here, we show that miR-199a promotes stem cell properties in mammary stem cells and breast CSCs by directly repressing nuclear receptor corepressor LCOR, which primes interferon (IFN) responses. Elevated miR-199a expression in stem-cell-enriched populations protects normal and malignant stem-like cells from differentiation and senescence induced by IFNs that are produced by epithelial and immune cells in the mammary gland. Importantly, the miR-199a-LCOR-IFN axis is activated in poorly differentiated ER- breast tumours, functionally promotes tumour initiation and metastasis, and is associated with poor clinical outcome. Our study therefore reveals a common mechanism shared by normal and malignant stem cells to protect them from suppressive immune cytokine signalling. |
