RUNX1 prevents oestrogen-mediated AXIN1 suppression and β-catenin activation in ER-positive breast cancer

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RUNX1 prevents oestrogen-mediated AXIN1 suppression and β-catenin activation in ER-positive breast cancer

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Title: RUNX1 prevents oestrogen-mediated AXIN1 suppression and β-catenin activation in ER-positive breast cancer
Author: Chimge, Nyam-Osor; Little, Gillian H.; Baniwal, Sanjeev K.; Adisetiyo, Helty; Xie, Ying; Zhang, Tian; O'Laughlin, Andie; Liu, Zhi Y.; Ulrich, Peaches; Martin, Anthony; Mhawech-Fauceglia, Paulette; Ellis, Matthew J.; Tripathy, Debu; Groshen, Susan; Liang, Chengyu; Li, Zhe; Schones, Dustin E.; Frenkel, Baruch

Note: Order does not necessarily reflect citation order of authors.

Citation: Chimge, N., G. H. Little, S. K. Baniwal, H. Adisetiyo, Y. Xie, T. Zhang, A. O'Laughlin, et al. 2016. “RUNX1 prevents oestrogen-mediated AXIN1 suppression and β-catenin activation in ER-positive breast cancer.” Nature Communications 7 (1): 10751. doi:10.1038/ncomms10751. http://dx.doi.org/10.1038/ncomms10751.
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Abstract: Recent high-throughput studies revealed recurrent RUNX1 mutations in breast cancer, specifically in oestrogen receptor-positive (ER+) tumours. However, mechanisms underlying the implied RUNX1-mediated tumour suppression remain elusive. Here, by depleting mammary epithelial cells of RUNX1 in vivo and in vitro, we demonstrate combinatorial regulation of AXIN1 by RUNX1 and oestrogen. RUNX1 and ER occupy adjacent elements in AXIN1's second intron, and RUNX1 antagonizes oestrogen-mediated AXIN1 suppression. Accordingly, RNA-seq and immunohistochemical analyses demonstrate an ER-dependent correlation between RUNX1 and AXIN1 in tumour biopsies. RUNX1 loss in ER+ mammary epithelial cells increases β-catenin, deregulates mitosis and stimulates cell proliferation and expression of stem cell markers. However, it does not stimulate LEF/TCF, c-Myc or CCND1, and it does not accelerate G1/S cell cycle phase transition. Finally, RUNX1 loss-mediated deregulation of β-catenin and mitosis is ameliorated by AXIN1 stabilization in vitro, highlighting AXIN1 as a potential target for the management of ER+ breast cancer.
Published Version: doi:10.1038/ncomms10751
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4773428/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:26318595
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