Loss of Fbxw7 synergizes with activated Akt signaling to promote c-Myc dependent cholangiocarcinogenesis
作者: Jingxiao WangHaichuan WangMichele PetersNing DingSilvia RibbackKirsten UtpatelAntonio CiglianoFrank DombrowskiMeng XuXinyan ChenXinhua SongLi CheMatthias EvertAntonio CossuJohn GordanYong ZengXin ChenDiego F. Calvisi
作者单位: 1School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China
2Department of Liver Surgery, Liver Transplantation Division, West China Hospital, Sichuan University, Chengdu, China
3Department of Bioengineering and Therapeutic Sciences and Liver Center, University of California, San Francisco, CA, United States
4Institute of Pathology, University of Greifswald, Greifswald, Germany
5Department of Gastroenterology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
6Institute of Pathology, University of Regensburg, Regensburg, Germany
7Department of General Surgery, The Second Hospital of Xi'an Jiaotong University, Xi'an Jiaotong University, Xi'an, China
8Department of Pharmacy, Hubei University of Chinese Medicine, Wuhan, China
9Unit of Pathology, Azienda Ospedaliero Universitaria Sassari, Sassari, Italy
10Department of Medicine, University of California, San Francisco, CA, United States
11Laboratory of Liver Surgery, West China Hospital, Sichuan University, Chengdu, China
刊名: Journal of Hepatology, 2019, Vol.71 (4), pp.742-752
来源数据库: Elsevier Journal
DOI: 10.1016/j.jhep.2019.05.027
关键词: FBXW7CholangiocarcinogenesisC-MycCholangiocarcinoma murine modelYapNotch2
英文摘要: Background & Aims(#br)The ubiquitin ligase F-box and WD repeat domain-containing 7 (FBXW7) is recognized as a tumor suppressor in many cancer types due to its ability to promote the degradation of numerous oncogenic target proteins. Herein, we aimed to elucidate its role in intrahepatic cholangiocarcinoma (iCCA).(#br)Methods(#br)Herein, we first confirmed that FBXW7 gene expression was reduced in human iCCA specimens. To identify the molecular mechanisms by which FBXW7 dysfunction promotes cholangiocarcinogenesis, we generated a mouse model by hydrodynamic tail vein injection of Fbxw7 ΔF, a dominant negative form of Fbxw7, either alone or in association with an activated/myristylated form of AKT (myr- AKT ). We then confirmed the role of c-MYC in human iCCA cell lines and its relationship...
全文获取路径: Elsevier  (合作)
影响因子:9.858 (2012)

  • murine 鼠灰色
  • signaling 发信号
  • promote 助长
  • dependent 从属的
  • activated 激化了的
  • model 模型