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Upholding a role for EMT in breast cancer metastasis

Nature volume 547, pages E1–E3 (2017)Cite this article

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arising from K. R. Fischer et al. Nature 527, 472–476 (2015); doi:10.1038/nature15748

The cell-biological program termed the epithelial-to-mesenchymal transition (EMT) has been invoked as a critical component of the metastatic process. Contrastingly, Fischer et al.1 recently reported that in two genetically engineered mouse models of mammary tumour development, carcinoma cells could metastasize without activating EMT programs. However, as detailed below, we find their evidence that EMT programs were not expressed in these primary tumours to be insufficient. Therefore, the contribution of EMT to carcinoma metastasis could not be ruled out in their analysis. There is a Reply to this Comment by Fischer, K. R. et al. Nature 547, 10.1038/nature22817 (2017).

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Figure 1: Fsp1 and vimentin are not universal markers of EMT programs in the MMTV-PyMT breast cancer model.

References

  1. Fischer, K. R. et al. Epithelial-to-mesenchymal transition is not required for lung metastasis but contributes to chemoresistance. Nature 527, 472–476 (2015)

    Article  ADS  CAS  Google Scholar 

  2. Tan, T. Z. et al. Epithelial-mesenchymal transition spectrum quantification and its efficacy in deciphering survival and drug responses of cancer patients. EMBO Mol. Med. 6, 1279–1293 (2014)

    Article  CAS  Google Scholar 

  3. Ye, X. et al. Distinct EMT programs control normal mammary stem cells and tumour-initiating cells. Nature 525, 256–260 (2015)

    Article  ADS  CAS  Google Scholar 

  4. Nieto, M. A., Huang, R. Y., Jackson, R. A. & Thiery, J. P. EMT: 2016. Cell 166, 21–45 (2016)

    Article  CAS  Google Scholar 

  5. Cano, A. et al. The transcription factor snail controls epithelial-mesenchymal transitions by repressing E-cadherin expression. Nat. Cell Biol. 2, 76–83 (2000)

    Article  CAS  Google Scholar 

  6. Batlle, E. et al. The transcription factor snail is a repressor of E-cadherin gene expression in epithelial tumour cells. Nat. Cell Biol. 2, 84–89 (2000)

    Article  CAS  Google Scholar 

  7. Comijn, J. et al. The two-handed E box binding zinc finger protein SIP1 downregulates E-cadherin and induces invasion. Mol. Cell 7, 1267–1278 (2001)

    Article  CAS  Google Scholar 

  8. Bolós, V. et al. The transcription factor Slug represses E-cadherin expression and induces epithelial to mesenchymal transitions: a comparison with Snail and E47 repressors. J. Cell Sci. 116, 499–511 (2003)

    Article  Google Scholar 

  9. Yang, J. et al. Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis. Cell 117, 927–939 (2004)

    Article  CAS  Google Scholar 

  10. Yu, M. et al. Circulating breast tumor cells exhibit dynamic changes in epithelial and mesenchymal composition. Science 339, 580–584 (2013)

    Article  ADS  CAS  Google Scholar 

  11. Grande, M. T. et al. Snail1-induced partial epithelial-to-mesenchymal transition drives renal fibrosis in mice and can be targeted to reverse established disease. Nat. Med. 21, 989–997 (2015)

    Article  CAS  Google Scholar 

  12. Ocaña, O. H. et al. Metastatic colonization requires the repression of the epithelial-mesenchymal transition inducer Prrx1. Cancer Cell 22, 709–724 (2012)

    Article  Google Scholar 

  13. Tsai, J. H., Donaher, J. L., Murphy, D. A., Chau, S. & Yang, J. Spatiotemporal regulation of epithelial-mesenchymal transition is essential for squamous cell carcinoma metastasis. Cancer Cell 22, 725–736 (2012)

    Article  CAS  Google Scholar 

  14. Tran, H. D. et al. Transient SNAIL1 expression is necessary for metastatic competence in breast cancer. Cancer Res. 74, 6330–6340 (2014)

    Article  CAS  Google Scholar 

  15. Beerling, E. et al. Plasticity between epithelial and mesenchymal states unlinks EMT from metastasis-enhancing stem cell capacity. Cell Reports 14, 2281–2288 (2016)

    Article  CAS  Google Scholar 

  16. Okada, H., Danoff, T. M., Kalluri, R. & Neilson, E. G. Early role of Fsp1 in epithelial-mesenchymal transformation. Am. J. Physiol. 273, F563–F574 (1997)

    Article  CAS  Google Scholar 

  17. Österreicher, C. H. et al. Fibroblast-specific protein 1 identifies an inflammatory subpopulation of macrophages in the liver. Proc. Natl Acad. Sci. USA 108, 308–313 (2011)

    Article  ADS  Google Scholar 

  18. Xue, C., Plieth, D., Venkov, C., Xu, C. & Neilson, E. G. The gatekeeper effect of epithelial-mesenchymal transition regulates the frequency of breast cancer metastasis. Cancer Res. 63, 3386–3394 (2003)

    CAS  PubMed  Google Scholar 

  19. Korpal, M. et al. Direct targeting of Sec23a by miR-200s influences cancer cell secretome and promotes metastatic colonization. Nat. Med. 17, 1101–1108 (2011)

    Article  CAS  Google Scholar 

  20. Ni, T. et al. Snail1-dependent p53 repression regulates expansion and activity of tumour-initiating cells in breast cancer. Nat. Cell Biol. 18, 1221–1232 (2016)

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Whitehead Institute for Biomedical Research, Cambridge, 02142, Massachusetts, USA

    Xin Ye & Robert A. Weinberg

  2. Ludwig/MIT Center for Molecular Oncology, Cambridge, 02142, Massachusetts, USA

    Xin Ye & Robert A. Weinberg

  3. Experimental Medicine I, Nikolaus-Fiebiger-Center for Molecular Medicine, FAU University of Erlangen-Nuernberg, Erlangen, 91054, Germany

    Thomas Brabletz

  4. Department of Molecular Biology, Princeton University, Princeton, 08544, New Jersey, USA

    Yibin Kang

  5. Departments of Medicine and Cell Biology and Physiology, ICCE Institute, Washington University, St Louis, 63110, Missouri, USA

    Gregory D. Longmore

  6. Instituto de Neurociencias Consejo Superior de Investigaciones Científicas and Universidad Miguel Hernández, San Juan de Alicante, Spain

    M. Angela Nieto

  7. Departments of Medicine and Cell and Developmental Biology, Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, 19104, Pennsylvania, USA

    Ben Z. Stanger

  8. Department of Pharmacology, Moores Cancer Center, University of California, San Diego, 3855 Health Sciences Drive, MC0819 La Jolla, California, 92093, USA

    Jing Yang

  9. Department of Biology, Massachusetts Institute of Technology, Cambridge, 02142, Massachusetts, USA

    Robert A. Weinberg

Authors
  1. Xin Ye
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  2. Thomas Brabletz
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  3. Yibin Kang
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  4. Gregory D. Longmore
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  5. M. Angela Nieto
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  7. Jing Yang
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Contributions

X.Y. produced and analysed the experimental data; T.B., Y.K., G.D.L., M.A.N., B.Z.S., J.Y. and R.A.W. conceived and wrote the manuscript.

Corresponding author

Correspondence to Robert A. Weinberg.

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Competing interests

R.A.W. is listed as an inventor on three patent applications filed by the Whitehead Institute for Biomedical Research relating to the formation of cancer stem cells through activation of an EMT program. US patent application number US 14/441,697 describes a method to use PKCa/FRA1 pathway inhibitors to target carcinoma cells that are identified by their increased expression of EMT-related genes. US patent application number US 15/307,657 describes a method to induce cancer stem cells to undergo EMT, rendering them amenable to conventional treatments. US patent application number US 14/065,311 describes methods for identifying compounds and compositions that target cancer stem cells, including cancer stem cells that have undergone EMT. R.A.W. is also listed as an inventor on two related patents that have been granted. US patent number US9212347 describes methods for preparing progenitor cells by inducing EMT. US patent number US9308238 describes methods and compounds for modulating and inducing EMT. R.A.W. is also a cofounder of Verastem Inc.

Extended data figures and tables

Extended Data Figure 1 Individual channels of the stained images shown in Fig. 1b, c.

a–d, DAPI nuclear staining is shown in blue. Anti-cytokeratin staining is shown in grey. Snail-expressing cells are marked by anti-YFP staining in green (a, b). Anti-Zeb1 staining is shown in green (c, d). Anti-Fsp1 (a, c) and anti-Vim (b, d) staining are shown in red. Arrows indicate cytokeratin-positive tumour cells that express either the Snail (a, b) or the Zeb1 (c, d) EMT transcription factor but, at the same time, lack evident Fsp1 (a, c) or Vim (b, d) expression. Scale bars, 20 μm.

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Ye, X., Brabletz, T., Kang, Y. et al. Upholding a role for EMT in breast cancer metastasis. Nature 547, E1–E3 (2017). https://doi.org/10.1038/nature22816

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