Normal and neoplastic non-stem cells can spontaneously convert to a stem-like state
Name
Weinberg-2011-May-Normal and neoplastic non-stem cells can spontaneously convert to a stem-like state.pdf
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1.2 MB
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Author(s)
Su, Ying
Polyak, Kornelia
Arendt, Lisa M.
Kuperwasser, Charlotte
Bierie, Brian
Chaffer, Christine L.
Brueckmann, Ines
Scheel, Christina
Kaestli, Alicia J.
Wiggins, Paul A.
Date Issued
April 2011
Journal
Proceedings of the National Academy of Sciences of the United States of America
Publisher
New York Academy of Sciences
Citation
Chaffer, C. L. et al. “Normal and neoplastic nonstem cells can spontaneously convert to a stem-like state.” Proceedings of the National Academy of Sciences 108 (2011): 7950-7955. Web. 2 Dec. 2011. © 2009 New York Academy of Sciences
Version
Final published version
Abstract
Current models of stem cell biology assume that normal and neoplastic stem cells reside at the apices of hierarchies and differentiate into nonstem progeny in a unidirectional manner. Here we identify a subpopulation of basal-like human mammary epithelial cells that departs from that assumption, spontaneously dedifferentiating into stem-like cells. Moreover, oncogenic transformation enhances the spontaneous conversion, so that nonstem cancer cells give rise to cancer stem cell (CSC)-like cells in vitro and in vivo. We further show that the differentiation state of normal cells-of-origin is a strong determinant of posttransformation behavior. These findings demonstrate that normal and CSC-like cells can arise de novo from more differentiated cell types and that hierarchical models of mammary stem cell biology should encompass bidirectional interconversions between stem and nonstem compartments. The observed plasticity may allow derivation of patient-specific adult stem cells without genetic manipulation and holds important implications for therapeutic strategies to eradicate cancer.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Biology
Whitehead Institute for Biomedical Research
Ludwig Center for Molecular Oncology (Massachusetts Institute of Technology)
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1073/pnas.1102454108
