| First Author | Zhang S | Year | 2020 |
| Journal | Am J Pathol | Volume | 190 |
| Issue | 7 | Pages | 1397-1413 |
| PubMed ID | 32283103 | Mgi Jnum | J:293310 |
| Mgi Id | MGI:6452549 | Doi | 10.1016/j.ajpath.2020.03.011 |
| Citation | Zhang S, et al. (2020) The Hippo Effector Transcriptional Coactivator with PDZ-Binding Motif Cooperates with Oncogenic beta-Catenin to Induce Hepatoblastoma Development in Mice and Humans. Am J Pathol 190(7):1397-1413 |
| abstractText | 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 (DeltaN90-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 DeltaN90-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-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/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. |
