Distinct and Overlapping Roles of Hippo Effectors YAP and TAZ During Human and Mouse HepatocarcinogenesisSummary
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...
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| Format: | Article |
| Language: | English |
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Elsevier
2021-01-01
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| Series: | Cellular and Molecular Gastroenterology and Hepatology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352345X20301879 |
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doaj-3e2b66d39a0349fc8c74647e42182481 |
|---|---|
| record_format |
Article |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Haichuan Wang Jingxiao Wang Shanshan Zhang Jiaoyuan Jia Xianqiong Liu Jie Zhang Pan Wang Xinhua Song Li Che Ke Liu Silvia Ribback Antonio Cigliano Matthias Evert Hong Wu Diego F. Calvisi Yong Zeng Xin Chen |
| spellingShingle |
Haichuan Wang Jingxiao Wang Shanshan Zhang Jiaoyuan Jia Xianqiong Liu Jie Zhang Pan Wang Xinhua Song Li Che Ke Liu Silvia Ribback Antonio Cigliano Matthias Evert Hong Wu Diego F. Calvisi Yong Zeng Xin Chen Distinct and Overlapping Roles of Hippo Effectors YAP and TAZ During Human and Mouse HepatocarcinogenesisSummary Cellular and Molecular Gastroenterology and Hepatology YAP TAZ Hepatocellular Carcinoma Cell Cycle |
| author_facet |
Haichuan Wang Jingxiao Wang Shanshan Zhang Jiaoyuan Jia Xianqiong Liu Jie Zhang Pan Wang Xinhua Song Li Che Ke Liu Silvia Ribback Antonio Cigliano Matthias Evert Hong Wu Diego F. Calvisi Yong Zeng Xin Chen |
| author_sort |
Haichuan Wang |
| title |
Distinct and Overlapping Roles of Hippo Effectors YAP and TAZ During Human and Mouse HepatocarcinogenesisSummary |
| title_short |
Distinct and Overlapping Roles of Hippo Effectors YAP and TAZ During Human and Mouse HepatocarcinogenesisSummary |
| title_full |
Distinct and Overlapping Roles of Hippo Effectors YAP and TAZ During Human and Mouse HepatocarcinogenesisSummary |
| title_fullStr |
Distinct and Overlapping Roles of Hippo Effectors YAP and TAZ During Human and Mouse HepatocarcinogenesisSummary |
| title_full_unstemmed |
Distinct and Overlapping Roles of Hippo Effectors YAP and TAZ During Human and Mouse HepatocarcinogenesisSummary |
| title_sort |
distinct and overlapping roles of hippo effectors yap and taz during human and mouse hepatocarcinogenesissummary |
| publisher |
Elsevier |
| series |
Cellular and Molecular Gastroenterology and Hepatology |
| issn |
2352-345X |
| publishDate |
2021-01-01 |
| description |
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. |
| topic |
YAP TAZ Hepatocellular Carcinoma Cell Cycle |
| url |
http://www.sciencedirect.com/science/article/pii/S2352345X20301879 |
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doaj-3e2b66d39a0349fc8c74647e421824812021-03-25T04:30:20ZengElsevierCellular and Molecular Gastroenterology and Hepatology2352-345X2021-01-0111410951117Distinct and Overlapping Roles of Hippo Effectors YAP and TAZ During Human and Mouse HepatocarcinogenesisSummaryHaichuan Wang0Jingxiao Wang1Shanshan Zhang2Jiaoyuan Jia3Xianqiong Liu4Jie Zhang5Pan Wang6Xinhua Song7Li Che8Ke Liu9Silvia Ribback10Antonio Cigliano11Matthias Evert12Hong Wu13Diego F. Calvisi14Yong Zeng15Xin Chen16Liver Transplantation Division, Department of Liver Surgery, Laboratory of Liver Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China; Department of Bioengineering and Therapeutic Sciences and Liver Center, University of California, San Francisco, CaliforniaDepartment of Bioengineering and Therapeutic Sciences and Liver Center, University of California, San Francisco, California; School of Life Sciences, Beijing University of Chinese Medicine, Beijing, ChinaDepartment of Bioengineering and Therapeutic Sciences and Liver Center, University of California, San Francisco, CaliforniaDepartment of Bioengineering and Therapeutic Sciences and Liver Center, University of California, San Francisco, California; Department of Oncology and Hematology, The Second Hospital, Jilin University, Changchun, ChinaDepartment of Bioengineering and Therapeutic Sciences and Liver Center, University of California, San Francisco, California; School of Pharmacy, Hubei University of Chinese Medicine Wuhan, Hubei, ChinaDepartment of Bioengineering and Therapeutic Sciences and Liver Center, University of California, San Francisco, CaliforniaDepartment of Bioengineering and Therapeutic Sciences and Liver Center, University of California, San Francisco, CaliforniaDepartment of Bioengineering and Therapeutic Sciences and Liver Center, University of California, San Francisco, CaliforniaDepartment of Bioengineering and Therapeutic Sciences and Liver Center, University of California, San Francisco, CaliforniaDepartment of Pediatrics and Human Development, East Lansing, Michigan; Department of Pharmacology and Toxicology, College of Human Medicine, Michigan State University, East Lansing, MichiganInstitute of Pathology, University of Greifswald, Greifswald, GermanyInstitute of Pathology, University Clinic of Regensburg, Regensburg, GermanyInstitute of Pathology, University Clinic of Regensburg, Regensburg, GermanyLiver Transplantation Division, Department of Liver Surgery, Laboratory of Liver Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of ChinaInstitute of Pathology, University Clinic of Regensburg, Regensburg, Germany; Correspondence Address correspondence to: Diego F. Calvisi, MD, Institute of Pathology, University of Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg, Germany. fax: (49) 941-994-6602.Liver Transplantation Division, Department of Liver Surgery, Laboratory of Liver Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China; Yong Zeng, MD, PhD, Department of Liver Surgery, Liver Transplantation Division, West China Hospital, Sichuan University, No. 37, Guo Xue Xiang, Chengdu, Sichuan 610041, China. fax: (86) 028-8542-2114.Department of Bioengineering and Therapeutic Sciences and Liver Center, University of California, San Francisco, California; Xin Chen, PhD, Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, California 94143. fax: (415) 502-4322.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.http://www.sciencedirect.com/science/article/pii/S2352345X20301879YAPTAZHepatocellular CarcinomaCell Cycle |