Poised Chromatin at the ZEB1 Promoter Enables Breast Cancer Cell Plasticity and Enhances Tumorigenicity
Name
Young_Poised chromatin.pdf
Size
983.02 KB
Format
Adobe PDF
Checksum (MD5)
17e0e0a18e612fbbf0ff0d6b6068aee4
Author(s)
Chaffer, Christine L.
Marjanovic, Nemanja D.
Lee, Tony
Bell, George
Kleer, Celina G.
Reinhardt, Ferenc
D’Alessio, Ana C.
Young, Richard A.
Weinberg, Robert A.
Young, Richard A.
Date Issued
July 2013
Journal
Cell
Publisher
Elsevier
Citation
Chaffer, Christine L., Nemanja D. Marjanovic, Tony Lee, George Bell, Celina G. Kleer, Ferenc Reinhardt, Ana C. D'Alessio, Richard A. Young, and Robert A. Weinberg. "Poised Chromatin at the ZEB1 Promoter Enables Breast Cancer Cell Plasticity and Enhances Tumorigenicity." Cell 154:1 (3 July 2013), pp. 61-74.
Version
Author's final manuscript
Abstract
The recent discovery that normal and neoplastic epithelial cells re-enter the stem cell state raised the intriguing possibility that the aggressiveness of carcinomas derives not from their existing content of cancer stem cells (CSCs) but from their proclivity to generate new CSCs from non-CSC populations. Here, we demonstrate that non-CSCs of human basal breast cancers are plastic cell populations that readily switch from a non-CSC to CSC state. The observed cell plasticity is dependent on ZEB1, a key regulator of the epithelial-mesenchymal transition. We find that plastic non-CSCs maintain the ZEB1 promoter in a bivalent chromatin configuration, enabling them to respond readily to microenvironmental signals, such as TGFβ. In response, the ZEB1 promoter converts from a bivalent to active chromatin configuration, ZEB1 transcription increases, and non-CSCs subsequently enter the CSC state. Our findings support a dynamic model in which interconversions between low and high tumorigenic states occur frequently, thereby increasing tumorigenic and malignant potential.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Whitehead Institute for Biomedical Research
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1016/j.cell.2013.06.005
