TY - JOUR TI - The histone H3K9 demethylase KDM3A promotes anoikis by transcriptionally activating pro-apoptotic genes BNIP3 and BNIP3L AU - Pedanou, Victoria E AU - Gobeil, Stéphane AU - Tabariès, Sébastien AU - Simone, Tessa M AU - Zhu, Lihua Julie AU - Siegel, Peter M AU - Green, Michael R A2 - Shilatifard, Ali VL - 5 PY - 2016 DA - 2016/07/29 SP - e16844 C1 - eLife 2016;5:e16844 DO - 10.7554/eLife.16844 UR - https://doi.org/10.7554/eLife.16844 AB - 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. KW - anoikis KW - BNIP3 KW - BNIP3L KW - KDM3A KW - histone demethylase JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -