Normal and cancerous mammary stem cells evade interferon-induced constraint through the miR-199a-LCOR axis

Citation:

Celià-Terrassa, Toni, et al. “Normal and cancerous mammary stem cells evade interferon-induced constraint through the miR-199a-LCOR axis”. Nat Cell Biol 19.6 (2017): , 19, 6, 711-723. Web.

Date Published:

2017 Jun

ISSN:

1476-4679

Abstract:

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 ERbreast 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.

DOI:

10.1038/ncb3533

Alternate Journal:

Nat. Cell Biol.