Wang, Haichuan and Wang, Jingxiao and Zhang, Shanshan and Jia, Jiaoyuan and Liu, Xianqiong and Zhang, Jie and Wang, Pan and Song, Xinhua and Che, Li and Liu, Ke and Ribback, Silvia and Cigliano, Antonio and Evert, Matthias and Wu, Hong and Calvisi, Diego F. and Zeng, Yong and Chen, Xin (2021) Distinct and Overlapping Roles of Hippo Effectors YAP and TAZ During Human and Mouse Hepatocarcinogenesis. CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY, 11 (4). pp. 1095-1117. ISSN 2352-345X,
Full text not available from this repository. (Request a copy)Abstract
BACKGROUND & AIMS: Yes-associated protein (YAP) and its paralog transcriptional co-activator with post synaptic density protein, drosophila disc large tumor suppressor and zonula occludens-1-binding motif (TAZ) are 2 co-activators downstream of Hippo tumor-suppressor cascade. Both have been implicated in the development of hepatocellular carcinoma (HCC). However, whether YAP and TAZ have distinct or overlapping functions during hepatocarcinogenesis remains unknown. METHODS: Expression patterns of YAP and TAZ were analyzed in human HCC samples. The requirement of Yap and/or Taz in protein kinase B (Akt)/ neuroblastoma RAS viral oncogene homolog (NRas)-driven liver tumorigenesis was analyzed using conditional Yap, Taz, and Yap;Taz knockout mice. Transcriptional programs regulated by YAP and/or TAZ were identified via RNA sequencing. RESULTS: We found that in human HCC samples, an almost ubiquitous activation of YAP or TAZ occurs, underlying their role in this tumor type. Intriguingly, 70% of HCC samples showed only nuclear YAP or TAZ immunoreactivity. In the Akt/NRas liver tumor model, where nuclear Yap and Taz can be detected readily, deletion of Yap or Taz alone only mildly delayed liver tumor development, whereas their concomitant ablation strongly inhibited tumor cell proliferation and significantly suppressed Akt/NRas-driven hepatocarcinogenesis. In HCC cell lines, silencing of either YAP or TAZ led to decreased expression of both overlapping and distinct sets of genes, with the most prominent gene signatures related to cell-cycle progression and DNA replication. CONCLUSIONS: YAP and TAZ have overlapping and distinct roles in hepatocarcinogenesis. HCCs may display unique activation of YAP or TAZ, thus relying on either YAP or TAZ for their growth.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | YES-ASSOCIATED PROTEIN; C-MYC; LIVER; CARCINOGENESIS; ACTIVATION; GENERATION; TARGET; YAP; TAZ; Hepatocellular Carcinoma; Cell Cycle |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 16 Sep 2022 15:39 |
| Last Modified: | 16 Sep 2022 15:39 |
| URI: | https://pred.uni-regensburg.de/id/eprint/47567 |
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