| GeneLibs

题目:: RUNX1 prevents oestrogen-mediated AXIN1 suppression and β-catenin activation in ER-positive breast cancer.
作者:: 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)
状态:: 发布时间2016-02-26 , 更新时间 2016-10-19
期刊:: Nat Commun
摘要:: 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.
语言:: eng
DOI:

文献库文献相关信息

DataTable pData

联系方式

微信公众号

文献库 文献相关信息

DataTable pData

联系方式

微信公众号

文献库文献相关信息