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Poised chromatin at the ZEB1 promoter enables breast cancer cell plasticity and enhances tumorigenicity.

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 TGF?. 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.

SUBMITTER: Chaffer CL

PROVIDER: S-EPMC4015106 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

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Poised chromatin at the ZEB1 promoter enables breast cancer cell plasticity and enhances tumorigenicity.

Chaffer Christine L CL Marjanovic Nemanja D ND Lee Tony T Bell George G Kleer Celina G CG Reinhardt Ferenc F D'Alessio Ana C AC Young Richard A RA Weinberg Robert A RA

Cell 20130701 1

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, ...[more]

PMID: 23827675

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Dataset Information

Poised chromatin at the ZEB1 promoter enables breast cancer cell plasticity and enhances tumorigenicity.

Publications

Poised chromatin at the ZEB1 promoter enables breast cancer cell plasticity and enhances tumorigenicity.

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