Feedback Activation of Leukemia Inhibitory Factor Receptor Limits Response to Histone Deacetylase Inhibitors in Breast Cancer

doi:10.1016/j.ccell.2016.08.001

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	Feedback Activation of Leukemia Inhibitory Factor Receptor Limits Response to Histone Deacetylase Inhibitors in Breast Cancer
	Zeng, Hanlin; Qu, Jia; Jin, Nan; Xu, Jun; Lin, Chenchu; Chen, Yi; Yang, Xinying; He, Xiang; Tang, Shuai; Lan, Xiaojing
刊名	CANCER CELL
	2016-09-12
卷号	30 期号:3 页码:459-473
ISSN号	1535-6108
DOI	10.1016/j.ccell.2016.08.001
文献子类	Article
英文摘要	Histone deacetylase (HDAC) inhibitors have demonstrated clinical benefits in subtypes of hematological malignancies. However, the efficacy of HDAC inhibitors in solid tumors remains uncertain. This study takes breast cancer as a model to understand mechanisms accounting for limited response of HDAC inhibitors in solid tumors and to seek combination solutions. We discover that feedback activation of leukemia inhibitory factor receptor (LIFR) signaling in breast cancer limits the response to HDAC inhibition. Mechanistically, HDAC inhibition increases histone acetylation at the LIFR gene promoter, which recruits bromodomain protein BRD4, upregulates LIFR expression, and activates JAK1-STAT3 signaling. Importantly, JAK1 or BRD4 inhibition sensitizes breast cancer to HDAC inhibitors, implicating combination inhibition of HDAC with JAK1 or BRD4 as potential therapies for breast cancer.
WOS关键词	PHASE-II TRIAL ; CONFERS RESISTANCE ; TUMOR XENOGRAFTS ; CONSTITUTIVE ACTIVATION ; SIGNALING PATHWAYS ; MULTIPLE-MYELOMA ; CELL LYMPHOMA ; STAT3 ; CYTOKINE ; APOPTOSIS
WOS研究方向	Oncology ; Cell Biology
语种	英语
出版者	CELL PRESS
WOS记录号	WOS:000383314200011
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/275893]
专题	药理学第一研究室中科院受体结构与功能重点实验室新药研究国家重点实验室
通讯作者	Huang, Min; Ding, Jian; Geng, Meiyu
作者单位	Chinese Acad Sci, Shanghai Inst Mat Med, Div Antitumor Pharmacol, State Key Lab Drug Res, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Zeng, Hanlin,Qu, Jia,Jin, Nan,et al. Feedback Activation of Leukemia Inhibitory Factor Receptor Limits Response to Histone Deacetylase Inhibitors in Breast Cancer[J]. CANCER CELL,2016,30(3):459-473.
APA	Zeng, Hanlin.,Qu, Jia.,Jin, Nan.,Xu, Jun.,Lin, Chenchu.,...&Geng, Meiyu.(2016).Feedback Activation of Leukemia Inhibitory Factor Receptor Limits Response to Histone Deacetylase Inhibitors in Breast Cancer.CANCER CELL,30(3),459-473.
MLA	Zeng, Hanlin,et al."Feedback Activation of Leukemia Inhibitory Factor Receptor Limits Response to Histone Deacetylase Inhibitors in Breast Cancer".CANCER CELL 30.3(2016):459-473.