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USP10 suppresses tumor progression by inhibiting mTOR activation in hepatocellular carcinoma

文献类型：期刊论文

作者Xia, Tian2; Tekcham, Dinesh Singh2; Wang, Wen2; Li, Tongming2; Liu, Xiumei2; Liu, Jing2; Qi, Huan2; Luo, Haifeng1; Du, Jian1; Ma, Chi1
刊名CANCER LETTERS
出版日期2018
卷号436页码:139-148
关键词HCC USP10 Deubiquitination mTOR
ISSN号0304-3835
DOI10.1016/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.
WOS关键词DEUBIQUITINATING ENZYMES ; CANCER-THERAPY ; PTEN ; STABILIZATION ; LOCALIZATION ; PATHWAY ; STATE ; TSC2 ; AKT ; P53
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研究方向Oncology
语种英语
WOS记录号WOS:000447095000014
出版者ELSEVIER IRELAND LTD
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
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.

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来源：大连化学物理研究所

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