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β-Catenin Sustains and Is Required for YES-associated Protein Oncogenic Activity in Cholangiocarcinoma.

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收录情况： ◇ SCIE

作者：
Yi Zhang[1,2] * ; Hongwei Xu[3] ; Guofei Cui[2] ; Binyong Liang[4] ; Xiangzheng Chen[5] ; Sungjin Ko[6] ; Silvia Affo[7] ; Xinhua Song[8] ; Yi Liao[9] ; Jianguo Feng[10,11] ; Pan Wang[12] ; Haichuan Wang[2,5] ; Meng Xu[13] ; Jingxiao Wang[14] ; Giovanni M. Pes[15] ; Silvia Ribback[16] ; Yong Zeng[5] ; Aatur Singhi[6] ; Robert F. Schwabe[17] ; Satdarshan P. Monga[6] ; Matthias Evert[18] ; Liling Tang[1,*1] ; Diego F. Calvisi[18,*2] ; Xin Chen[2,19,*3] ;
机构： [1]Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, ChongqingUniversity, Chongqing, China [2]Department of Bioengineering and Therapeutic Sciences and Liver Center, University ofCalifornia, San Francisco, California, USA [3]Department of Liver Surgery, Center of Liver Transplantation, West China Hospitalof Sichuan University, Chengdu, Sichuan, China [4]Hepatic Surgery Center, Department of Surgery, Tongji Hospital, TongjiMedical College, Huazhong University of Science and Technology, Wuhan, China [5]Liver Transplantation Division, Departmentof Liver Surgery, and Laboratory of Liver Surgery, West China Hospital, Sichuan University, Chengdu, China [6]Department ofPathology and Medicine, and Pittsburgh Liver Research Center, University of Pittsburgh School of Medicine, and University ofPittsburgh Medical Center, Pittsburgh, Pennsylvania, USA [7]Institut d’Investigacions Biomèdiques August Pi i Sunyer(IDIBAPS), Barcelona, Spain [8]School of Traditional Chinese Medicine, Capital Medical University, Beijing, China [9]The CentralLaboratory, Shenzhen Second People’s Hospital/First Affiliated Hospital of Shenzhen University Health Science Center,Shenzhen, Guangdong, China [10]Department of Anesthesiology, The Affiliated Hospital of Southwest Medical University,Luzhou, China [11]Laboratory of Anesthesiology, Southwest Medical University, Luzhou, China [12]Collaborative InnovationCenter for Agricultural Product Processing and Nutrition & Health, Beijing Vegetable Research Center, Beijing Academy ofAgriculture and Forestry Science, Beijing, China [13]Department of General Surgery, The Second Affiliated Hospital of Xi’anJiaotong University, Xi’an Jiaotong University, Xi’an, China [14]School of Life Sciences, Beijing University of Chinese Medicine,Beijing, China [15]Department of Medical, Surgical, and Experimental Sciences, University of Sassari, Sassari, Italy [16]Institute ofPathology, University of Greifswald, Greifswald, Germany [17]Department of Medicine, Columbia University, New York, NewYork, USA [18]Institute of Pathology, University of Regensburg, Regensburg, Germany [19]Cancer Biology Program, University ofHawaii Cancer Center, Honolulu, Hawaii, USA
出处：
DOI： 10.1053/j.gastro.2022.04.028
ISSN：

关键词： b-Catenin Hippo/YAP Intrahepatic Cholangiocarcinoma TEADs

摘要：
YES-associated protein (YAP) aberrant activation is implicated in intrahepatic cholangiocarcinoma (iCCA). Transcriptional enhanced associate domain (TEAD)-mediated transcriptional regulation is the primary signaling event downstream of YAP. The role of Wnt/β-Catenin signaling in cholangiocarcinogenesis remains undetermined. Here, we investigated the possible molecular interplay between YAP and β-Catenin cascades in iCCA.Activated Akt (Myr-Akt) was coexpressed with Yap (YapS127A) or Tead2VP16 via hydrodynamic tail vein injection into mouse livers. Tumor growth was monitored, and liver tissues were collected and analyzed using histopathologic and molecular analysis. Yap, β-Catenin, and TEAD interaction in iCCAs was investigated through coimmunoprecipitation. Conditional Ctnnb1 knockout mice were used to determine β-Catenin function in murine iCCA models. RNA sequencing was performed to analyze the genes regulated by YAP and/or β-Catenin. Immunostaining of total and nonphosphorylated/activated β-Catenin staining was performed in mouse and human iCCAs.We discovered that TEAD factors are required for YAP-dependent iCCA development. However, transcriptional activation of TEADs did not fully recapitulate YAP's activities in promoting cholangiocarcinogenesis. Notably, β-Catenin physically interacted with YAP in human and mouse iCCA. Ctnnb1 ablation strongly suppressed human iCCA cell growth and Yap-dependent cholangiocarcinogenesis. Furthermore, RNA-sequencing analysis revealed that YAP/ transcriptional coactivator with PDZ-binding motif (TAZ) regulate a set of genes significantly overlapping with those controlled by β-Catenin. Importantly, activated/nonphosphorylated β-Catenin was detected in more than 80% of human iCCAs.YAP induces cholangiocarcinogenesis via TEAD-dependent transcriptional activation and interaction with β-Catenin. β-Catenin binds to YAP in iCCA and is required for YAP full transcriptional activity, revealing the functional crosstalk between YAP and β-Catenin pathways in cholangiocarcinogenesis.Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.

基金：
R01CA19606 (to Xin Chen) and R01CA228483 (to Xin Chen and Robert F. Schwabe); R01CA204586 and R01CA250227 (to Xin Chen and Satdarshan P. Monga), P30DK026743 (to Xin Chen by UCSF Liver Center), P30DK120531 (to Satdarshan P. Monga by the Pittsburgh Liver Research Center), and R01CA258449 (to Sungjin Ko).
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外文
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中科院(CAS)分区：
出版当年[2022]版：
大类 | 1 区 医学
小类 | 1 区 胃肠肝病学
最新[2023]版：
大类 | 1 区 医学
小类 | 1 区 胃肠肝病学
JCR分区：
出版当年[2022]版：
Q1 GASTROENTEROLOGY & HEPATOLOGY
最新[2023]版：
Q1 GASTROENTEROLOGY & HEPATOLOGY

影响因子： 最新[2023版] 最新五年平均 出版当年[2022版] 出版当年五年平均 出版前一年[2021版] 出版后一年[2023版]

第一作者：
第一作者机构： [1]Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, ChongqingUniversity, Chongqing, China [2]Department of Bioengineering and Therapeutic Sciences and Liver Center, University ofCalifornia, San Francisco, California, USA
通讯作者：
通讯机构： [1]Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, ChongqingUniversity, Chongqing, China [2]Department of Bioengineering and Therapeutic Sciences and Liver Center, University ofCalifornia, San Francisco, California, USA [18]Institute of Pathology, University of Regensburg, Regensburg, Germany [19]Cancer Biology Program, University ofHawaii Cancer Center, Honolulu, Hawaii, USA [*1]Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China [*2]Institute of Pathology, University of Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg, Germany [*3]Cancer Biology Program, University of Hawaii Cancer Center, Honolulu, Hawaii 96813
推荐引用方式(GB/T 7714)：
Yi Zhang,Hongwei Xu,Guofei Cui,et al.β-Catenin Sustains and Is Required for YES-associated Protein Oncogenic Activity in Cholangiocarcinoma.[J].GASTROENTEROLOGY.2022,163(2):481-494.doi:10.1053/j.gastro.2022.04.028.
APA：
Yi Zhang,Hongwei Xu,Guofei Cui,Binyong Liang,Xiangzheng Chen...&Xin Chen.(2022).β-Catenin Sustains and Is Required for YES-associated Protein Oncogenic Activity in Cholangiocarcinoma..GASTROENTEROLOGY,163,(2)
MLA：
Yi Zhang,et al."β-Catenin Sustains and Is Required for YES-associated Protein Oncogenic Activity in Cholangiocarcinoma.".GASTROENTEROLOGY 163..2(2022):481-494

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