A suppressor mutation that creates

TitleA suppressor mutation that creates
Publication TypeJournal Article
Year of Publication2017
AuthorsCelià-Terrassa, T, Liu, DD, Choudhury, A, Hang, X, Wei, Y, Zamalloa, J, Alfaro-Aco, R, Chakrabarti, R, Jiang, Y-Z, Koh, BIhn, Smith, HA, DeCoste, C, Li, J-J, Shao, Z-M, Kang, Y
JournalNat Cell Biol
Volume19
Issue6
Pagination711-723
Date Published2017 Jun
ISSN1476-4679
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 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.

DOI10.1038/ncb3533
Alternate JournalNat. Cell Biol.
PubMed ID28530657
PubMed Central IDPMC5481166
Grant ListP30 CA072720 / CA / NCI NIH HHS / United States
R01 CA141062 / CA / NCI NIH HHS / United States