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The Hippo Effector Transcriptional Coactivator with PDZ-Binding Motif Cooperates with Oncogenic β-Catenin to Induce Hepatoblastoma Development in Mice and Humans.

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收录情况： ◇ SCIE

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机构： [1]Cancer Center and State Key Laboratory of Biotherapy,West China Hospital, Sichuan University, Chengdu, PR China [2]Lung Cancer Center,West China Hospital, Sichuan University, Chengdu, PR China [3]Department of Bioengineering and Therapeutic Sciences and Liver Center,University of California, San Francisco, San Francisco, California [4]the Department of Thoracic Oncology II, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University Cancer Hospital and Institute, Beijing, PR China [5]the Institute of Pathology, University of Regensburg, Regensburg, Germany [6]the Department of Thyroid and Breast Surgery, The 960th Hospital of the PLA, Jinan, PR China [7]the Department of Pediatrics, Zhongnan Hospital of Wuhan University, Wuhan, PR China [8]the Second Department of Pathology, Semmelweis University, Budapest, Hungary [9]the Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, PR China [10]Department of Medical, Surgical, and Experimental Sciences, [11]Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania

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Hepatoblastoma (HB) is the most common pediatric liver tumor. Though Wnt/β-catenin and Hippo cascades are implicated in HB development, studies on crosstalk between β-catenin and Hippo downstream effector transcriptional coactivator with PDZ-binding motif (TAZ) in HB are lacking. Expression levels of TAZ and β-catenin in human HB specimens were assessed by IHC. Functional interplay between TAZ and β-catenin was determined by overexpression of an activated form of TAZ (TAZS89A), either alone or combined with an oncogenic form of β-catenin (ΔN90-β-catenin), in mouse liver via hydrodynamic transfection. We found that activation of TAZ often co-occurred with that of β-catenin in clinical specimens. While overexpression of TAZS89A alone did not induce hepatocarcinogenesis, concomitant overexpression of TAZS89A and ΔN90-β-catenin triggered the development of HB lesions exhibiting both epithelial and mesenchymal features. Mechanistically, TAZ/β-catenin-driven HB development required TAZ interaction with transcriptional enhanced associate domain factors. Blockade of the Notch cascade did not inhibit TAZ/β-catenin-dependent HB formation in mice but suppressed the mesenchymal phenotype. Neither Yes-associated protein nor heat shock factor 1 depletion affected HB development in TAZ/β-catenin mice. In human HB cell lines, silencing of TAZ resulted in decreased cell growth, which was further reduced when TAZ knockdown was associated with suppression of either β-catenin or Yes-associated protein. Overall, our study identified TAZ as a crucial oncogene in HB development and progression. Copyright © 2020 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

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出版当年[2020]版：

Q2 PATHOLOGY

最新[2023]版：

Q1 PATHOLOGY

影响因子： 4.7 最新[2023版] 4.8 最新五年平均 4.307 出版当年[2020版] 5.138 出版当年五年平均 3.491 出版前一年[2019版] 5.77 出版后一年[2021版]

第一作者：

第一作者机构： [1]Cancer Center and State Key Laboratory of Biotherapy,West China Hospital, Sichuan University, Chengdu, PR China [3]Department of Bioengineering and Therapeutic Sciences and Liver Center,University of California, San Francisco, San Francisco, California

通讯作者：

通讯机构： [10]Department of Medical, Surgical, and Experimental Sciences, [11]Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania [*1]University of Pittsburgh School of Medicine, 200 Lothrop St. S-432 BST, Pittsburgh, PA 15261 [*2]Department of Medical, Surgical, and Experimental Sciences,University of Sassari, via P.Manzella 4, Sassari 07100, Italy

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