Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Reducing interferon'ce in stem cells

Nature Cell Biology volume 19, pages 597–599 (2017)Cite this article

Subjects

Little is known regarding how the interactions of stem cells with the immune system regulate their plasticity. A study now describes a mechanism by which normal breast and cancer stem cells utilize miR-199a to downregulate the corepressor LCOR and minimize responses to type I interferon.

The mammary epithelium is composed of two main lineages: luminal epithelial cells and basal myoepithelial cells, named for their location around the ductal lumen or the basal position near the basement membrane, respectively1. Of these, the basal lineage (identified as CD49fhiCD29hiCD24+/modSca1low) contains a population of mammary stem cells and is strongly associated with triple-negative breast cancer (TNBC), hinting that an improved understanding of the stem cell phenotype may have clinical implications in breast cancer1,2. Numerous microRNAs (miRNAs) have been shown to regulate the process of self-renewal and differentiation in stem cells3. For the most part this has been ascribed to regulation of critical target genes directly responsible for these processes, with comparatively less attention paid to the role of miRNAs in modulating the interaction of stem cells with their niche4. Accordingly, although the immune system is an important regulator of tissue homeostasis, little is known regarding the impact of inflammatory cytokines on stem cell properties during tissue regeneration or cancer5. In this issue of Nature Cell Biology, Celià-Terrassa et al.6 describe a conserved mechanism by which normal mammary and breast cancer stem cells alter their responses to inflammatory mediators through expression of miR-199a. Specifically, they identify that a miR-199a–LCOR (ligand-dependent nuclear receptor corepressor) axis regulates cellular responses to type I interferon (IFN).

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Learn more

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Regulation of stemness by controlling cellular responses to type I IFNs through the miR-199a–LCOR axis.

References

  1. Visvader, J. E. & Clevers, H. Nat. Cell Biol. 18, 349–355 (2016).

    Article  CAS  PubMed  Google Scholar 

  2. Visvader, J. E. & Stingl, J. Genes Dev. 28, 1143–1158 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Shenoy, A. & Blelloch, R. H. Nat. Rev. Mol. Cell Biol. 15, 565–576 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Gangaraju, V. K. & Lin, H. Nat. Rev. Mol. Cell Biol. 10, 116–125 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Aurora, A. B. & Olson, E. N. Cell Stem Cell 15, 14–25 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Celià-Terrassa, T. et al. Nat. Cell Biol. 19, 711–723 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  7. O'Brien, J. et al. Am. J. Pathol. 176, 1241–1255 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Cheng, W., Liu, T., Wan, X., Gao, Y. & Wang, H. FEBS J. 279, 2047–2059 (2012).

    Article  CAS  PubMed  Google Scholar 

  9. Liu, R. et al. Oncotarget 7, 56628–56642 (2016).

    PubMed  PubMed Central  Google Scholar 

  10. Hu, Y. et al. Dig. Dis. Sci. 59, 2163–2172 (2014).

    Article  CAS  PubMed  Google Scholar 

  11. Zitvogel, L., Galluzzi, L., Kepp, O., Smyth, M. J. & Kroemer, G. Nat. Rev. Immunol. 15, 405–414 (2015).

    Article  CAS  PubMed  Google Scholar 

  12. Chen, H. M. et al. Cancer Sci. 100, 449–456 (2009).

    Article  CAS  PubMed  Google Scholar 

  13. Maccalli, C., Volontè, A., Cimminiello, C. & Parmiani, G. Eur. J. Cancer 50, 649–655 (2014).

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, 33612, Florida, USA

    Alycia Gardner & Brian Ruffell

  2. Cancer Biology PhD Program, University of South Florida, Tampa, 33620, Florida, USA

    Alycia Gardner

  3. Department of Breast Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, 33612, Florida, USA

    Brian Ruffell

Authors
  1. Alycia Gardner
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Brian Ruffell
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Brian Ruffell.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and Permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gardner, A., Ruffell, B. Reducing interferon'ce in stem cells. Nat Cell Biol 19, 597–599 (2017). https://doi.org/10.1038/ncb3544

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ncb3544

Search

Advanced search

Quick links

Nature Briefing: Cancer

Sign up for the Nature Briefing: Cancer newsletter — what matters in cancer research, free to your inbox weekly.

Get what matters in cancer research, free to your inbox weekly. Sign up for Nature Briefing: Cancer