The Epithelial-Mesenchymal Transition Generates Cells with Properties of Stem Cells

Sendurai A. Mani, Wenjun Guo, Mai Jing Liao, Elinor Ng Eaton, Ayyakkannu Ayyanan, Alicia Y. Zhou, Mary Brooks, Ferenc Reinhard, Cheng Cheng Zhang, Michail Shipitsin, Lauren L. Campbell, Kornelia Polyak, Cathrin Brisken, Jing Yang, Robert A. Weinberg

Research output: Contribution to journalArticle

5658 Scopus citations

Abstract

The epithelial-mesenchymal transition (EMT) is a key developmental program that is often activated during cancer invasion and metastasis. We here report that the induction of an EMT in immortalized human mammary epithelial cells (HMLEs) results in the acquisition of mesenchymal traits and in the expression of stem-cell markers. Furthermore, we show that those cells have an increased ability to form mammospheres, a property associated with mammary epithelial stem cells. Independent of this, stem cell-like cells isolated from HMLE cultures form mammospheres and express markers similar to those of HMLEs that have undergone an EMT. Moreover, stem-like cells isolated either from mouse or human mammary glands or mammary carcinomas express EMT markers. Finally, transformed human mammary epithelial cells that have undergone an EMT form mammospheres, soft agar colonies, and tumors more efficiently. These findings illustrate a direct link between the EMT and the gain of epithelial stem cell properties.

Original languageEnglish (US)
Pages (from-to)704-715
Number of pages12
JournalCell
Volume133
Issue number4
DOIs
StatePublished - May 16 2008
Externally publishedYes

Keywords

  • CELLBIO
  • HUMDISEASE
  • STEMCELL

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Mani, S. A., Guo, W., Liao, M. J., Eaton, E. N., Ayyanan, A., Zhou, A. Y., Brooks, M., Reinhard, F., Zhang, C. C., Shipitsin, M., Campbell, L. L., Polyak, K., Brisken, C., Yang, J., & Weinberg, R. A. (2008). The Epithelial-Mesenchymal Transition Generates Cells with Properties of Stem Cells. Cell, 133(4), 704-715. https://doi.org/10.1016/j.cell.2008.03.027