Disordered signaling governing ferroportin transcription favors breast cancer growth

CORC > 生态环境研究中心 > 中国科学院生态环境研究中心 > 环境化学与生态毒理学国家重点实验室

	Disordered signaling governing ferroportin transcription favors breast cancer growth
	Chen, Yue; Zhang, Shuping; Wang, Xiaoyan; Guo, Wenli; Wang, Lei; Zhang, Daoqiang; Yuan, Lin; Zhang, Zhihong; Xu, Yong; Liu, Sijin
刊名	CELLULAR SIGNALLING
	2015-01
卷号	27 期号:1 页码:168-176
关键词	Iron FPN Transcriptional regulation Nrf2 MZF-1 Methylation
英文摘要	Iron is a necessary chemical element needed by all organisms. Iron metabolism is finely tuned in mammals, and the hepcidin-ferroportin (FPN) axis is the central signaling in governing systemic iron homeostasis. Deregulation of this signaling would lead to iron disorders and likely other diseases including cancers. Reduced FPN was previously found to correlate with poor prognosis in breast cancer patients. Nonetheless, the biological effects of abnormal FPN expression in tumor cells remain largely unexplored, and the mechanisms underlying misregulated expression of FPN in cancers keep elusive. In the current study, we scrutinized the effects of abnormal FPN on tumor growth and the molecular mechanisms of diminished tumor FPN. Downregulation of FPN significantly promoted breast cancer growth, whereas FPN upregulation impeded tumor growth. We demonstrated that the transcription factors Nrf2 (nuclear factor erythroid 2-like 2) and MZF-1 (myeloid zinc finger-1) synergistically transactivated FPN expression in breast cancer cells. Moreover, CpG island methylation at the FPN promoter was the reason of attenuated FPN expression. Downregulation of Nrf2 and MZF-1 and hypermethylation of the FPN promoter were concurrently associated with decreased FPN concentration in breast tumors. Taken together, our study highlighted the contribution of disordered iron metabolism to breast cancer growth, and also signified an oncogenic effect of misregulated ferroportin in breast cancers. This work represents a promising starting point to the possibility of restraining breast cancer through targeting FPN or its upstream regulatory factors. (C) 2014 Elsevier Inc All rights reserved.
研究领域[WOS]	Cell Biology
WOS记录号	WOS:000347508300017
公开日期	2016-03-15
内容类型	期刊论文
源URL	[http://ir.rcees.ac.cn/handle/311016/32556]
专题	生态环境研究中心_环境化学与生态毒理学国家重点实验室
推荐引用方式 GB/T 7714	Chen, Yue,Zhang, Shuping,Wang, Xiaoyan,et al. Disordered signaling governing ferroportin transcription favors breast cancer growth[J]. CELLULAR SIGNALLING,2015,27(1):168-176.
APA	Chen, Yue.,Zhang, Shuping.,Wang, Xiaoyan.,Guo, Wenli.,Wang, Lei.,...&Liu, Sijin.(2015).Disordered signaling governing ferroportin transcription favors breast cancer growth.CELLULAR SIGNALLING,27(1),168-176.
MLA	Chen, Yue,et al."Disordered signaling governing ferroportin transcription favors breast cancer growth".CELLULAR SIGNALLING 27.1(2015):168-176.