@article{111196,
  keywords = {Animals, Humans, signal transduction, Gene Expression Profiling, Transcription Factors, Repressor Proteins, Cell Proliferation, HeLa Cells, MicroRNAs, Phenotype, Mice, Inbred C57BL, Female, Cell Movement, Mice, Transgenic, Breast Neoplasms, Gene Expression Regulation, Neoplastic, Cell Differentiation, Transfection, Cell Transformation, Neoplastic, Mammary Glands, Human, HEK293 Cells, Interferons, Neoplasm Metastasis, Neoplastic Stem Cells, Tumor Microenvironment, MCF-7 Cells, Mammary Glands, Animal, Cell Self Renewal},
  author = {Toni Celi{\`a}-Terrassa and Daniel Liu and Abrar Choudhury and Xiang Hang and Yong Wei and Jose Zamalloa and Raymundo Alfaro-Aco and Rumela Chakrabarti and Yi-Zhou Jiang and Bong Ihn Koh and Heath Smith and Christina DeCoste and Jun-Jing Li and Zhi-Ming Shao and Yibin Kang},
  title = {Normal and cancerous mammary stem cells evade interferon-induced constraint through the miR-199a-LCOR axis},
  abstract = {<p>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.</p>
},
  year = {2017},
  journal = {Nat Cell Biol},
  volume = {19},
  pages = {711-723},
  month = {06/2017},
  issn = {1476-4679},
  doi = {10.1038/ncb3533},
  language = {eng},
}