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

作者：Celia-Terrassa, Toni; Liu, Daniel D.; Choudhury, Abrar; Hang, Xiang; Wei, Yong; Zamalloa, Jose; Alfaro-Aco, Raymundo; Chakrabarti, Rumela; Jiang, Yi-Zhou; Koh, Bong Ihn; Smith, Heath A.; DeCoste, Christina; Li, Jun-Jing; Shao, Zhi-Ming; Kang, Yibin^*

来源：Nature Cell Biology, 2017, 19(6): 711-+.

DOI：10.1038/ncb3533

• EPITHELIAL-MESENCHYMAL TRANSITION
• GENE-EXPRESSION SIGNATURE
• NEGATIVE BREAST-CANCER
• INTEGRATED MESSENGER-RNA
• MOLECULAR CHARACTERIZATION
• RECEPTOR COREPRESSOR
• GLAND DEVELOPMENT
• INITIATING CELLS
• IMMUNE ESCAPE
• I INTERFERONS

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.

• 出版日期2017-6
• 单位复旦大学