DICP OpenIR
USP10 suppresses tumor progression by inhibiting mTOR activation in hepatocellular carcinoma
Lu, Chang1,2; Ning, Zhen1,2; Wang, Aman1; Ghen, Di2; Liu, Xiaolong2; Xia, Tian2; Tekcham, Dinesh Singh2; Wang, Wen2; Li, Tongming2; Liu, Xiumei2; Liu, Jing2; Qi, Huan2; Luo, Haifeng1; Du, Jian1; Ma, Chi1; Yan, Qiu1; Liu, Jiwei1; Xu, Guowang2; Piao, Hai-long2; Tan, Guang1
Corresponding AuthorPiao, Hai-long(HPiao@dicp.ac.cn) ; Tan, Guang(tanguang@firsthosp-dmu.com)
KeywordHCC USP10 Deubiquitination mTOR
Source PublicationCANCER LETTERS
2018
ISSN0304-3835
DOI10.1016/j.canlet.2018.07.032
Volume436Pages:139-148
Funding ProjectNational 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
Funding OrganizationNational 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
WOS SubjectOncology
WOS Research AreaOncology
WOS KeywordDEUBIQUITINATING ENZYMES ; CANCER-THERAPY ; PTEN ; STABILIZATION ; LOCALIZATION ; PATHWAY ; STATE ; TSC2 ; AKT ; P53
AbstractDysregulation 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.
Language英语
Funding OrganizationNational 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
WOS IDWOS:000447095000014
PublisherELSEVIER IRELAND LTD
Citation statistics
Cited Times:2[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://cas-ir.dicp.ac.cn/handle/321008/166881
Collection中国科学院大连化学物理研究所
Corresponding AuthorPiao, Hai-long; Tan, Guang
Affiliation1.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
Recommended Citation
GB/T 7714
Lu, Chang,Ning, Zhen,Wang, Aman,et al. USP10 suppresses tumor progression by inhibiting mTOR activation in hepatocellular carcinoma[J]. CANCER LETTERS,2018,436:139-148.
APA Lu, Chang.,Ning, Zhen.,Wang, Aman.,Ghen, Di.,Liu, Xiaolong.,...&Tan, Guang.(2018).USP10 suppresses tumor progression by inhibiting mTOR activation in hepatocellular carcinoma.CANCER LETTERS,436,139-148.
MLA Lu, Chang,et al."USP10 suppresses tumor progression by inhibiting mTOR activation in hepatocellular carcinoma".CANCER LETTERS 436(2018):139-148.
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