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Editorial
. 2013 Sep 1;12(17):2713-4.
doi: 10.4161/cc.26075. Epub 2013 Aug 19.

Poised with purpose: cell plasticity enhances tumorigenicity

Nemanja D Marjanovic  1 , Robert A Weinberg, Christine L Chaffer
Affiliations
Editorial

Poised with purpose: cell plasticity enhances tumorigenicity

Nemanja D Marjanovic et al. Cell Cycle. .
No abstract available

Keywords: EMT; ZEB1; bivalent chromatin; breast cancer; cancer stem cell; cell plasticity; non-cancer stem cell.

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Figure 1. Cancer stem cells (CSCs) were thought to adhere to a unidirectional hierarchical model where CSCs reside at the apex undergoing symmetric division to replenish the CSC pool or asymmetric division to generate non-CSC progeny. New evidence suggests that the CSC model is not unidirectional, rather non-CSCs can ascend the cellular hierarchy and re-enter the CSC state. Here we show that among breast cancer cells, basal-type non-CSCs are particularly proficient at generating CSCs. Switching from the non-CSC to CSC state is dependent on activation of the transcription factor ZEB1, and can be enhanced by the addition of factors such as TGFβ. Basal non-CSCs are readily able to activate ZEB1 due to the maintenance of its promoter in a bivalent chromatin configuration. In this formation, the ZEB1 promoter is marked simultaneously by repressive (H3K27me3) and activating (H3K4me3) histone modifications. In response to the appropriate signals, H3K27me3 is removed from the ZEB1 promoter, enabling the active H3K4me3 mark to persist and thereafter, presumably, foster active transcription of this gene.
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