Journal
NATURE CELL BIOLOGY
Volume 19, Issue 6, Pages 711-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ncb3533
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Funding
- Susan G. Komen Fellowship [PDF15332075]
- Brewster Foundation
- Breast Cancer Research Foundation
- Department of Defense [BC123187]
- National Institutes of Health [R01CA141062]
- Genomic Editing and Flow Cytometry Shared Resources of the Cancer Institute of New Jersey [P30CA072720]
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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.
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