Utility of the dual-specificity protein kinase TTK as a therapeutic target for intrahepatic spread of liver cancer

doi:10.1038/srep33121

	Utility of the dual-specificity protein kinase TTK as a therapeutic target for intrahepatic spread of liver cancer
	Miao, Ruoyu 1,2,3,4; Wu, Yan 3,4; Zhang, Haohai 1,2; Zhou, Huandi 5,6; Sun, Xiaofeng 3,4; Csizmadia, Eva 3,4; He, Lian 1,2; Zhao, Yi 7; Jiang, Chengyu 5,6; Miksad, Rebecca A.8; Ghaziani, Tahereh 3,4; Robson, Simon C.3,4; Zhao, Haitao 1,2
	2016-09-13
发表期刊	SCIENTIFIC REPORTS
ISSN	2045-2322
卷号	6 页码:13
摘要	Therapies for primary liver cancer, the third leading cause of cancer-related death worldwide, remain limited. Following multi-omics analysis (including whole genome and transcriptome sequencing), we were able to identify the dual-specific protein kinase TTK as a putative new prognostic biomarker for liver cancer. Herein, we show that levels of TTK protein are significantly elevated in neoplastic tissues from a cohort of liver cancer patients, when compared with adjacent hepatic tissues. We also tested the utility of TTK targeted inhibition and have demonstrated therapeutic potential in an experimental model of liver cancer in vivo. Following lentiviral shRNA knockdown in several human liver cancer cell lines, we demonstrated that TTK boosts cell growth and promotes cell spreading; as well as protects against senescence and decreases autophagy. In an experimental animal model, we show that in vitro knockdown of TTK effectively blocks intrahepatic growth of human HCC xenografts. Furthermore, we note that, in vivo silencing of TTK, by systemically delivering TTK siRNAs to already tumor-bearing liver, limits intrahepatic spread of liver cancer cells. This intervention is associated with decreased tumor aggressiveness, as well as increased senescence and autophagy. Taken together, our data suggest that targeted TTK inhibition might have clinical utility as an adjunct therapy in management of liver cancer.
DOI	10.1038/srep33121
收录类别	SCI
语种	英语
资助项目	NIH[P01HL107152-01] ; NIH[R21 CA164970] ; Ben and Rose Cole PRIA Foundation ; Pancreatic Cancer Research Fund ; International Science and Technology Cooperation Projects[2015DFA30650] ; Capital Special Research Project for Health Development[2014-2-4012] ; Capital Research Project for the Characteristics Clinical Application[Z151100004015170]
WOS研究方向	Science & Technology - Other Topics
WOS类目	Multidisciplinary Sciences
WOS记录号	WOS:000382932000001
出版者	NATURE PUBLISHING GROUP
引用统计	被引频次：34[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://119.78.100.204/handle/2XEOYT63/8182
专题	中国科学院计算技术研究所期刊论文_英文
通讯作者	Robson, Simon C.; Zhao, Haitao
作者单位	1.Chinese Acad Med Sci, Peking Union Med Coll Hosp, Dept Liver Surg, Beijing 100730, Peoples R China 2.Peking Union Med Coll, Beijing 100730, Peoples R China 3.Harvard Med Sch, Beth Israel Deaconess Med Ctr, Ctr Liver, Boston, MA 02115 USA 4.Harvard Med Sch, Beth Israel Deaconess Med Ctr, Transplant Inst, Dept Med, Boston, MA 02115 USA 5.Chinese Acad Med Sci, State Key Lab Med Mol Biol, Inst Basic Med Sci, Beijing 100005, Peoples R China 6.Peking Union Med Coll, Beijing 100005, Peoples R China 7.Chinese Acad Sci, Inst Comp Technol, Key Lab Intelligent Informat Proc, Beijing 100190, Peoples R China 8.Harvard Med Sch, Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Dept Med, Boston, MA 02115 USA
推荐引用方式 GB/T 7714	Miao, Ruoyu,Wu, Yan,Zhang, Haohai,et al. Utility of the dual-specificity protein kinase TTK as a therapeutic target for intrahepatic spread of liver cancer[J]. SCIENTIFIC REPORTS,2016,6:13.
APA	Miao, Ruoyu.,Wu, Yan.,Zhang, Haohai.,Zhou, Huandi.,Sun, Xiaofeng.,...&Zhao, Haitao.(2016).Utility of the dual-specificity protein kinase TTK as a therapeutic target for intrahepatic spread of liver cancer.SCIENTIFIC REPORTS,6,13.
MLA	Miao, Ruoyu,et al."Utility of the dual-specificity protein kinase TTK as a therapeutic target for intrahepatic spread of liver cancer".SCIENTIFIC REPORTS 6(2016):13.