UMMS Affiliation

Department of Molecular, Cell and Cancer Biology

Date

7-29-2016

Document Type

Article

Disciplines

Bioinformatics | Cancer Biology | Cell Biology

Abstract

Epithelial cells that lose attachment to the extracellular matrix undergo a specialized form of apoptosis called anoikis. Here, using large-scale RNA interference (RNAi) screening, we find that KDM3A, a histone H3 lysine 9 (H3K9) mono- and di-demethylase, plays a pivotal role in anoikis induction. In attached breast epithelial cells, KDM3A expression is maintained at low levels by integrin signaling. Following detachment, integrin signaling is decreased resulting in increased KDM3A expression. RNAi-mediated knockdown of KDM3A substantially reduces apoptosis following detachment and, conversely, ectopic expression of KDM3A induces cell death in attached cells. We find that KDM3A promotes anoikis through transcriptional activation of BNIP3 and BNIP3L, which encode pro-apoptotic proteins. Using mouse models of breast cancer metastasis we show that knockdown of Kdm3a enhances metastatic potential. Finally, we find defective KDM3A expression in human breast cancer cell lines and tumors. Collectively, our results reveal a novel transcriptional regulatory program that mediates anoikis.

Rights and Permissions

The version of the article available for download is the authors' final, peer-reviewed accepted manuscript as prepared for publication in: Elife. 2016 Jul 29;5. pii: e16844. doi: 10.7554/eLife.16844. Link to article on publisher's site

Copyright © 2016, Pedanou et al. This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

DOI of Published Version

10.7554/eLife.16844

Related Resources

Link to Article in PubMed

Keywords

cell biology, chromosomes, genes, human, mouse

Journal Title

eLife

PubMed ID

27472901

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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