PMID- 35729702
OWN - NLM
STAT- MEDLINE
DCOM- 20221006
LR  - 20230124
IS  - 1600-6143 (Electronic)
IS  - 1600-6135 (Linking)
VI  - 22
IP  - 10
DP  - 2022 Oct
TI  - E2F7 promotes mammalian target of rapamycin inhibitor resistance in 
      hepatocellular carcinoma after liver transplantation.
PG  - 2323-2336
LID - 10.1111/ajt.17124 [doi]
AB  - The mammalian target of rapamycin (mTOR) pathway is frequently deregulated and 
      has critical roles in cancer progression. mTOR inhibitor has been widely used in 
      several kinds of cancers and is strongly recommended in patients with 
      hepatocellular carcinoma (HCC) after liver transplantation (LT). However, the 
      poor response to mTOR inhibitors due to resistance remains a challenge. 
      Hypoxia-associated resistance limits the therapeutic efficacy of targeted drugs. 
      The present study established models of HCC clinical samples and cell lines 
      resistance to mTOR inhibitor sirolimus and screened out E2F7 as a candidate gene 
      induced by hypoxia and promoting sirolimus resistance. E2F7 suppressed mTOR 
      complex 1 via directly binding to the promoter of the TSC1 gene and stabilizes 
      hypoxia-inducible factor-1alpha activating its downstream genes, which are 
      responsible for E2F7-dependent mTOR inhibitor resistance. Clinically, low E2F7 
      expression could be an effective biomarker for recommending patients with HCC for 
      anti-mTOR-based therapies after LT. Targeting E2F7 synergistically inhibited HCC 
      growth with sirolimus in vivo. E2F7 is a promising target to reverse mTOR 
      inhibition resistance. Collectively, our study points to a role for E2F7 in 
      promoting mTOR inhibitor resistance in HCC and emphasizes its potential clinical 
      significance in patients with HCC after LT.
CI  - (c) 2022 The American Society of Transplantation and the American Society of 
      Transplant Surgeons.
FAU - Ling, Sunbin
AU  - Ling S
AUID- ORCID: 0000-0003-0846-5489
AD  - Department of Hepatobiliary and Pancreatic Surgery, The Center for Integrated 
      Oncology and Precision Medicine, Affiliated Hangzhou First People's Hospital, 
      Zhejiang University School of Medicine, Hangzhou, China.
AD  - Zhejaing University, School of Medicine, Hangzhou, China.
AD  - Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang 
      Province, Hangzhou, China.
AD  - Institute of Organ Transplantation, Zhejiang University, Hangzhou, China.
FAU - Zhan, Qifan
AU  - Zhan Q
AD  - Department of Hepatobiliary and Pancreatic Surgery, The Center for Integrated 
      Oncology and Precision Medicine, Affiliated Hangzhou First People's Hospital, 
      Zhejiang University School of Medicine, Hangzhou, China.
AD  - Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang 
      Province, Hangzhou, China.
FAU - Jiang, Guangjiang
AU  - Jiang G
AD  - Department of Hepatobiliary and Pancreatic Surgery, The Center for Integrated 
      Oncology and Precision Medicine, Affiliated Hangzhou First People's Hospital, 
      Zhejiang University School of Medicine, Hangzhou, China.
AD  - Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang 
      Province, Hangzhou, China.
FAU - Shan, Qiaonan
AU  - Shan Q
AD  - Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated 
      Hospital, Zhejiang University School of Medicine, Hangzhou, China.
FAU - Yin, Lu
AU  - Yin L
AD  - Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang 
      Province, Hangzhou, China.
FAU - Wang, Rui
AU  - Wang R
AD  - Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang 
      Province, Hangzhou, China.
FAU - Que, Qingyang
AU  - Que Q
AD  - Department of Hepatobiliary and Pancreatic Surgery, The Center for Integrated 
      Oncology and Precision Medicine, Affiliated Hangzhou First People's Hospital, 
      Zhejiang University School of Medicine, Hangzhou, China.
AD  - Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang 
      Province, Hangzhou, China.
FAU - Wei, Xuyong
AU  - Wei X
AD  - Department of Hepatobiliary and Pancreatic Surgery, The Center for Integrated 
      Oncology and Precision Medicine, Affiliated Hangzhou First People's Hospital, 
      Zhejiang University School of Medicine, Hangzhou, China.
AD  - Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang 
      Province, Hangzhou, China.
FAU - Xu, Shengjun
AU  - Xu S
AD  - Department of Hepatobiliary and Pancreatic Surgery, The Center for Integrated 
      Oncology and Precision Medicine, Affiliated Hangzhou First People's Hospital, 
      Zhejiang University School of Medicine, Hangzhou, China.
FAU - Yu, Jiongjie
AU  - Yu J
AD  - Department of Hepatobiliary and Pancreatic Surgery, The Center for Integrated 
      Oncology and Precision Medicine, Affiliated Hangzhou First People's Hospital, 
      Zhejiang University School of Medicine, Hangzhou, China.
AD  - Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang 
      Province, Hangzhou, China.
FAU - Zhou, Wei
AU  - Zhou W
AD  - Department of Hepatobiliary and Pancreatic Surgery, The Center for Integrated 
      Oncology and Precision Medicine, Affiliated Hangzhou First People's Hospital, 
      Zhejiang University School of Medicine, Hangzhou, China.
AD  - Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang 
      Province, Hangzhou, China.
FAU - Zhang, Lincheng
AU  - Zhang L
AD  - Department of Hepatobiliary and Pancreatic Surgery, The Center for Integrated 
      Oncology and Precision Medicine, Affiliated Hangzhou First People's Hospital, 
      Zhejiang University School of Medicine, Hangzhou, China.
AD  - Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang 
      Province, Hangzhou, China.
FAU - Bao, Jiaqi
AU  - Bao J
AD  - Department of Hepatobiliary and Pancreatic Surgery, The Center for Integrated 
      Oncology and Precision Medicine, Affiliated Hangzhou First People's Hospital, 
      Zhejiang University School of Medicine, Hangzhou, China.
AD  - Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang 
      Province, Hangzhou, China.
FAU - Ye, Qianwei
AU  - Ye Q
AD  - Department of Hepatobiliary and Pancreatic Surgery, The Center for Integrated 
      Oncology and Precision Medicine, Affiliated Hangzhou First People's Hospital, 
      Zhejiang University School of Medicine, Hangzhou, China.
FAU - Su, Renyi
AU  - Su R
AD  - Department of Hepatobiliary and Pancreatic Surgery, The Center for Integrated 
      Oncology and Precision Medicine, Affiliated Hangzhou First People's Hospital, 
      Zhejiang University School of Medicine, Hangzhou, China.
AD  - Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang 
      Province, Hangzhou, China.
FAU - Wei, Rongli
AU  - Wei R
AD  - Department of Hepatobiliary and Pancreatic Surgery, The Center for Integrated 
      Oncology and Precision Medicine, Affiliated Hangzhou First People's Hospital, 
      Zhejiang University School of Medicine, Hangzhou, China.
AD  - Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang 
      Province, Hangzhou, China.
FAU - Liu, Jimin
AU  - Liu J
AD  - Department of Pathology and Molecular Medicine, Faculty of Health Sciences, 
      McMaster University, Hamilton, Ontario, Canada.
FAU - Chen, Kangchen
AU  - Chen K
AD  - Department of Hepatobiliary and Pancreatic Surgery, The Center for Integrated 
      Oncology and Precision Medicine, Affiliated Hangzhou First People's Hospital, 
      Zhejiang University School of Medicine, Hangzhou, China.
FAU - Wang, Jingrui
AU  - Wang J
AD  - Department of Hepatobiliary and Pancreatic Surgery, The Center for Integrated 
      Oncology and Precision Medicine, Affiliated Hangzhou First People's Hospital, 
      Zhejiang University School of Medicine, Hangzhou, China.
FAU - Xie, Haiyang
AU  - Xie H
AD  - Institute of Organ Transplantation, Zhejiang University, Hangzhou, China.
AD  - Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated 
      Hospital, Zhejiang University School of Medicine, Hangzhou, China.
FAU - Zheng, Shusen
AU  - Zheng S
AUID- ORCID: 0000-0003-1459-8261
AD  - Institute of Organ Transplantation, Zhejiang University, Hangzhou, China.
AD  - Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated 
      Hospital, Zhejiang University School of Medicine, Hangzhou, China.
AD  - Department of Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital, 
      Hangzhou, China.
FAU - He, Xin
AU  - He X
AD  - Key Laboratory of Tropical Disease Control of Ministry of Education, Guangdong 
      Engineering Research Center for Antimicrobial Agent and Immunotechnology, 
      Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-Sen 
      University, Guangzhou, China.
FAU - Xiang, Jiajia
AU  - Xiang J
AD  - ZJU-Hangzhou Global Scientific and Technological Innovation Center, Hangzhou, 
      China.
FAU - Xu, Xiao
AU  - Xu X
AUID- ORCID: 0000-0002-2761-2811
AD  - Zhejaing University, School of Medicine, Hangzhou, China.
AD  - Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang 
      Province, Hangzhou, China.
AD  - Institute of Organ Transplantation, Zhejiang University, Hangzhou, China.
AD  - Westlake Laboratory, Life Sciences and Biomedicine, Hangzhou, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220701
PL  - United States
TA  - Am J Transplant
JT  - American journal of transplantation : official journal of the American Society of 
      Transplantation and the American Society of Transplant Surgeons
JID - 100968638
RN  - 0 (E2F7 Transcription Factor)
RN  - 0 (E2F7 protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (MTOR Inhibitors)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - *Carcinoma, Hepatocellular/drug therapy/surgery
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - E2F7 Transcription Factor
MH  - Humans
MH  - Hypoxia/drug therapy
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/pharmacology/therapeutic use
MH  - *Liver Neoplasms/drug therapy/surgery
MH  - *Liver Transplantation
MH  - MTOR Inhibitors
MH  - Sirolimus/pharmacology
MH  - TOR Serine-Threonine Kinases
OTO - NOTNLM
OT  - E2F7
OT  - drug resistance
OT  - hepatocellular carcinoma
OT  - mTOR inhibitor
EDAT- 2022/06/22 06:00
MHDA- 2022/10/07 06:00
CRDT- 2022/06/21 23:48
PHST- 2022/06/13 00:00 [revised]
PHST- 2022/03/16 00:00 [received]
PHST- 2022/06/13 00:00 [accepted]
PHST- 2022/06/22 06:00 [pubmed]
PHST- 2022/10/07 06:00 [medline]
PHST- 2022/06/21 23:48 [entrez]
AID - S1600-6135(22)29937-7 [pii]
AID - 10.1111/ajt.17124 [doi]
PST - ppublish
SO  - Am J Transplant. 2022 Oct;22(10):2323-2336. doi: 10.1111/ajt.17124. Epub 2022 Jul 
      1.