Distinct EMT programs control normal mammary stem cells and tumour-initiating cells

  • Ye X
  • Tam W
  • Shibue T
 et al. 
  • 422


    Mendeley users who have this article in their library.
  • 148


    Citations of this article.


Tumour-initiating cells (TICs) are responsible for metastatic dissemination and clinical relapse in a variety of cancers1,2 . Analogies between TICs and normal tissue stem cells have led to the proposal that activation of the normal stem-cell programwithin a tissue serves as the major mechanism for generating TICs3–7 . Supporting this notion, we and others previously established that the Slug epithelial-to-mesenchymal transition-inducing transcrip- tion factor (EMT-TF), a member of the Snail family, serves as a master regulator of the gland-reconstituting activity of normal mammary stem cells, and that forced expression of Slug in collab- oration with Sox9 in breast cancer cells can efficiently induce entrance into the TIC state8 . However, these earlier studies focused on xenograft models with cultured cell lines and involved ectopic expression of EMT-TFs, often at non-physiological levels. Using genetically engineered knock-in reportermouse lines, here we show thatnormalgland-reconstitutingmammary stemcells9–11 residingin the basal layer of the mammary epitheliumand breast TICs origin- ating in the luminal layer exploit the paralogous EMT-TFs Slug and Snail, respectively, which induce distinct EMT programs. Broadly, our findings suggest that the seemingly similar stem-cell programs operating in TICs and normal stemcells of the corresponding nor- mal tissue are likely to differ significantly in their details.

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document


Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free