ROCK1 Inhibition Promotes the Self-Renewal of a Novel Mouse Mammary Cancer Stem Cell§


  • Author contributions: D.C. and J.M.: conception and design, collection and/or assembly of data, data analysis and interpretation, manuscript writing; L.H.: collection and/or assembly of data; R.O.: conception and design, data analysis and interpretation, manuscript writing, and final approval of manuscript. D.J.C. and J.M. contributed equally to this article.

  • Disclosure of potential conflicts of interest is found at the end of this article.

  • §

    First published online in STEM CELLSEXPRESS September 7, 2012.


The differentiation of stem-like tumor cells may contribute to the cellular heterogeneity of breast cancers. We report the propagation of highly enriched mouse mammary cancer stem cells that retain the potential to differentiate both in vivo and in culture and their use to identify chemical compounds that influence both self-renewal and differentiation. We identify epithelial tumor-initiating cells (ETICs) that express lineage markers of both basal and luminal mammary cell lineages and retain the potential, from even single cells, to generate heterogeneous tumors similar to the tumor of origin. ETICs can progress through a Rho-associated coiled-coil containing protein kinase 1 dependent, epithelial to mesenchymal transition to generate mesenchymal tumor-initiating cells capable of initiating tumors of limited heterogeneity. The propagation of ETICs may allow for the identification of new therapeutic compounds that may inhibit or prevent progression of some types of breast cancer. Stem Cells2013;31:12–22