USP10 suppresses tumor progression by inhibiting mTOR activation in hepatocellular carcinoma

doi:10.1016/j.canlet.2018.07.032

	USP10 suppresses tumor progression by inhibiting mTOR activation in hepatocellular carcinoma
	Xia, Tian 2; Tekcham, Dinesh Singh 2; Wang, Wen 2; Li, Tongming 2; Liu, Xiumei 2; Liu, Jing 2; Qi, Huan 2; Luo, Haifeng 1; Du, Jian 1; Ma, Chi 1
刊名	CANCER LETTERS
	2018
卷号	436 页码:139-148
关键词	HCC USP10 Deubiquitination mTOR
ISSN号	0304-3835
DOI	10.1016/j.canlet.2018.07.032
通讯作者	Piao, Hai-long(HPiao@dicp.ac.cn) ; Tan, Guang(tanguang@firsthosp-dmu.com)
英文摘要	Dysregulation of deubiquitination pathway is associated with poor prognosis in cancers such as hepatocellular carcinoma (HCC). The mammalian target of rapamycin, mTOR, has become an attractive cancer therapeutic target in HCC. However, whether and how aberrant expression of deubiquitination pathway regulates mTOR pathway has remained elusive. Here we report that ubiquitin-specific protease 10 (USP10) functions as a tumor suppressor which inhibits mTOR pathway by stabilizing PTEN and AMPK alpha in HCC cells. Mechanistically, USP10 interacts and stabilizes PTEN and AMPK alpha by inhibiting their polyubiquitylation. This stabilization in turn inhibits AKT phosphorylation and mTOR Complexl (mTORC1) activation. In human liver cancer, USP10 expression is downregulated in HCC tumor tissues across three independent HCC cohorts, and lower-expression of USP10 will generate poor prognosis outcome. Collectively, our results uncover an undescribed mechanism where USP10, as a tumor suppressor, negatively regulates mTORC1 activation and AKT phosphorylation by stabilizing AMPKa and PTEN in HCC cells. This study sheds light on the theoretical basis of mTOR signaling pathwayoriented targeting treatment in clinic.
资助项目	National Key Research and Development Program of China[2016YFC0903302] ; National Natural Science Foundation of China[81502024] ; National Natural Science Foundation of China[81672440] ; National Natural Science Foundation of China[31701156] ; Innovation program of science and research from the DICP, CAS[DICP TMSR201601] ; 100 Talents Program of Chinese Academy of Sciences
WOS关键词	DEUBIQUITINATING ENZYMES ; CANCER-THERAPY ; PTEN ; STABILIZATION ; LOCALIZATION ; PATHWAY ; STATE ; TSC2 ; AKT ; P53
WOS研究方向	Oncology
语种	英语
出版者	ELSEVIER IRELAND LTD
WOS记录号	WOS:000447095000014
资助机构	National Key Research and Development Program of China ; National Key Research and Development Program of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; Innovation program of science and research from the DICP, CAS ; Innovation program of science and research from the DICP, CAS ; 100 Talents Program of Chinese Academy of Sciences ; 100 Talents Program of Chinese Academy of Sciences ; National Key Research and Development Program of China ; National Key Research and Development Program of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; Innovation program of science and research from the DICP, CAS ; Innovation program of science and research from the DICP, CAS ; 100 Talents Program of Chinese Academy of Sciences ; 100 Talents Program of Chinese Academy of Sciences ; National Key Research and Development Program of China ; National Key Research and Development Program of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; Innovation program of science and research from the DICP, CAS ; Innovation program of science and research from the DICP, CAS ; 100 Talents Program of Chinese Academy of Sciences ; 100 Talents Program of Chinese Academy of Sciences ; National Key Research and Development Program of China ; National Key Research and Development Program of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; Innovation program of science and research from the DICP, CAS ; Innovation program of science and research from the DICP, CAS ; 100 Talents Program of Chinese Academy of Sciences ; 100 Talents Program of Chinese Academy of Sciences
内容类型	期刊论文
源URL	[http://cas-ir.dicp.ac.cn/handle/321008/166880]
专题	大连化学物理研究所_中国科学院大连化学物理研究所
通讯作者	Piao, Hai-long; Tan, Guang
作者单位	1.Dalian Med Univ, Affiliated Hosp 1, Dalian 116000, Peoples R China 2.Chinese Acad Sci, Sci Res Ctr Translat Med, Dalian Inst Chem Phys, CAS Key Lab Separat Sci Analyt Chem, Dalian 116023, Peoples R China
推荐引用方式 GB/T 7714	Xia, Tian,Tekcham, Dinesh Singh,Wang, Wen,et al. USP10 suppresses tumor progression by inhibiting mTOR activation in hepatocellular carcinoma[J]. CANCER LETTERS,2018,436:139-148.
APA	Xia, Tian.,Tekcham, Dinesh Singh.,Wang, Wen.,Li, Tongming.,Liu, Xiumei.,...&Liu, Xiaolong.(2018).USP10 suppresses tumor progression by inhibiting mTOR activation in hepatocellular carcinoma.CANCER LETTERS,436,139-148.
MLA	Xia, Tian,et al."USP10 suppresses tumor progression by inhibiting mTOR activation in hepatocellular carcinoma".CANCER LETTERS 436(2018):139-148.