演題抄録

FACO Poster Session

開催概要
開催回
第56回・2018年・横浜
 

USP10 suppresses tumor progression by stabilizing PTEN and AMPKa in hepatocellular carcinoma cells

演題番号 : FP1-28

[筆頭演者]
Speaker)Chang Lu:1,2 
[共同演者]
Zhen Ning:1,2、Aman Wang:3、Di Chen:2、Guang Tan:1、Hailong Piao:2

1:Department of Hepatobiliary Surgery, 1st Affliated Hospital of Dalian Medical University, China、2:scientific reasearch center for translational medicine, Dalian Institute of Chemical Physics Chinese Academy of Sciences, China、3:Oncology Department, 1st Affliated Hospital of Dalian Medical University, China

 

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 AMPKa in HCC cells. Mechanistically, USP10 interacts and stabilizes PTEN and AMPKα by inhibiting their polyubiquitylation. This stabilization in turn inhibits AKT phosphorylation and mTOR Complex1 (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 pathway-oriented targeting treatment in clinic.

キーワード

臓器別:Liver

手法別:Basic Oncology

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