Zhang, Shu and Zhang, Jie and Evert, Katja and Li, Xiaolei and Liu, Pin and Kiss, Andras and Schaff, Zsuzsa and Ament, Cindy and Zhang, Yi and Serra, Monica and Evert, Matthias and Chen, Nianyong and Xu, Feng and Chen, Xin and Tao, and Calvisi, Diego F. and Cigliano, Antonio (2020) The Hippo Effector Transcriptional Coactivator with PDZ-Binding Motif Cooperates with Oncogenic beta-Catenin to Induce Hepatoblastoma Development in Mice and Humans. AMERICAN JOURNAL OF PATHOLOGY, 190 (7). pp. 1397-1413. ISSN 0002-9440, 1525-2191
Full text not available from this repository. (Request a copy)Abstract
Hepatoblastoma (HB) is the most common pediatric liver tumor. Though Wnt/beta-catenin and Hippo cascades are implicated in HB development, studies on crosstalk between beta-catenin and Hippo downstream effector transcriptional coactivator with PDZ-binding motif (TAZ) in HB are lacking. Expression levels of TAZ and beta-catenin in human HB specimens were assessed by immunohistochemistry. Functional interplay between TAZ and beta-catenin was determined by overexpression of an activated form of TAZ (TAZS89A), either alone or combined with an oncogenic form of beta-catenin (Delta N90-beta-catenin), in mouse liver via hydrodynamic transfection. Activation of TAZ often co-occurred with that of beta-catenin in clinical specimens. Although the overexpression of TAZS89A alone did not induce hepatocarcinogenesis, concomitant overexpression of TAZS89A and Delta N90-beta-catenin triggered the development of HB lesions exhibiting both epithelial and mesenchymal features. Mechanistically, TAZ/beta-catenin-driven HB development required TAZ interaction with transcriptional enhanced associate domain factors. Blockade of the Notch cascade did not inhibit TAZ/beta-cateninedependent HB formation in mice but suppressed the mesenchymal phenotype. Neither Yes-associated protein nor heat shock factor 1 depletion affected HB development in TAZ/beta-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 beta-catenin or Yes-associated protein. Overall, our study identified TAZ as a crucial oncogene in HB development and progression.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | TUMOR-SUPPRESSOR; GENOMIC ANALYSIS; MOUSE MODELS; LIVER; PATHWAY; TRANSFECTION; HOMEOSTASIS; GROWTH; TAZ; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 19 Mar 2021 11:02 |
| Last Modified: | 19 Mar 2021 11:02 |
| URI: | https://pred.uni-regensburg.de/id/eprint/44313 |
Actions (login required)
 |
View Item |
