HSPC111 Governs Breast Cancer Growth by Regulating Ribosomal Biogenesis

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

	HSPC111 Governs Breast Cancer Growth by Regulating Ribosomal Biogenesis
	Zhang, Changwen ; Yin, Chunyang ; Wang, Lei ; Zhang, Shuping ; Qian, Yi ; Ma, Juan ; Zhang, Zhihong ; Xu, Yong ; Liu, Sijin
刊名	MOLECULAR CANCER RESEARCH
	2014
卷号	12 期号:4 页码:583-594
ISSN号	1541-7786
中文摘要	Activation of c-Myc plays a decisive role in the development of many human cancers. As a transcription factor, c-Myc facilitates cell growth and proliferation by directly transcribing a multitude of targets, including rRNAs and ribosome proteins. However, how to elucidate the deregulation of rRNAs and ribosome proteins driven by c-Myc in cancer remains a significant challenge and thus warrants close investigation. In this report, a crucial role for the HSPC111 (NOP16) multiprotein complex in governing ribosomal biogenesis and tumor growth was determined. It was discovered that enhanced HSPC111 expression paralleled the upregulation of c-Myc and was directly regulated by c-Myc in breast cancer cells. Knockdown of HSPC111 dramatically reduced the occurrence of tumorigenesis in vivo, and largely restrained tumor cell growth in vitro and in vivo. In stark contrast, HSPC111 overexpression significantly promoted tumor cell growth. Biochemically, it was demonstrated that RNA 3'-phosphate cyclase (RTCD1/RTCA) interacted with HSPC111, and RTCD1 was involved in the HSPC111 multiprotein complex in regulating rRNA production and ribosomal biogenesis. Moreover, HSPC111 and RTCD1 synergistically modulated cell growth and cellular size through commanding rRNA synthesis and ribosome assembly coupled to protein production. Finally, overall survival analysis revealed that concomitant upregulation of HSPC111 and RTCD1 correlated with the worst prognosis in a breast cancer cohort. Implications: Inhibition of HSPC111-dependent ribosomal biosynthesis and protein synthesis is a promising therapeutic strategy to diminish breast cancer tumor progression. (C) 2014 AACR.
WOS记录号	WOS:000334583900011
公开日期	2015-03-24
内容类型	期刊论文
源URL	[http://ir.rcees.ac.cn/handle/311016/9383]
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	Zhang, Changwen,Yin, Chunyang,Wang, Lei,et al. HSPC111 Governs Breast Cancer Growth by Regulating Ribosomal Biogenesis[J]. MOLECULAR CANCER RESEARCH,2014,12(4):583-594.
APA	Zhang, Changwen.,Yin, Chunyang.,Wang, Lei.,Zhang, Shuping.,Qian, Yi.,...&Liu, Sijin.(2014).HSPC111 Governs Breast Cancer Growth by Regulating Ribosomal Biogenesis.MOLECULAR CANCER RESEARCH,12(4),583-594.
MLA	Zhang, Changwen,et al."HSPC111 Governs Breast Cancer Growth by Regulating Ribosomal Biogenesis".MOLECULAR CANCER RESEARCH 12.4(2014):583-594.