The DOI matches its Crossref record; 43 of the 43 references it cites were found in a registry or an index.
The Hippo–Salvador pathway restrains hepatic oval cell proliferation, liver size, and liver tumorigenesis
Open accessAbstract
Loss of Hippo signaling in Drosophila leads to tissue overgrowth as a result of increased cell proliferation and decreased cell death. YAP (a homolog of Drosophila Yorkie and target of the Hippo pathway) was recently implicated in control of organ size, epithelial tissue development, and tumorigenesis in mammals. However, the role of the mammalian Hippo pathway in such regulation has remained unclear. We now show that mice with liver-specific ablation of WW45 (a homolog of Drosophila Salvador and adaptor for the Hippo kinase) manifest increased liver size and expansion of hepatic progenitor cells (oval cells) and eventually develop hepatomas. Moreover, ablation of WW45 increased the abundance of YAP and induced its localization to the nucleus in oval cells, likely accounting for their increased proliferative capacity, but not in hepatocytes. Liver tumors that developed in mice heterozygous for WW45 deletion or with liver-specific WW45 ablation showed a mixed pathology combining characteristics of hepatocellular carcinoma and cholangiocarcinoma and seemed to originate from oval cells. Together, our results suggest that the mammalian Hippo–Salvador pathway restricts the proliferation of hepatic oval cells and thereby controls liver size and prevents the development of oval cell–derived tumors.
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Cites
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Self-citationTEAD mediates YAP-dependent gene induction and growth control
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Cited by
Hippo pathway in organ size control, tissue homeostasis, and cancer
Yu, F.-X., Zhao, B., & Guan, K.-L. (2015) · Cell · doi:10.1016/j.cell.2015.10.044 · Cited by 2,206
The Hippo Signaling Pathway in Development and Cancer
Pan, D. (2010) · Developmental Cell · doi:10.1016/j.devcel.2010.09.011 · Cited by 2,269
YAP/TAZ at the Roots of Cancer
Zanconato, F., Cordenonsi, M., & Piccolo, S. (2016) · Cancer Cell · doi:10.1016/j.ccell.2016.05.005 · Cited by 1,970
Mechanisms of Hippo pathway regulation
Meng, Z., Moroishi, T., & Guan, K.-L. (2016) · Genes & Development · doi:10.1101/gad.274027.115 · Cited by 1,667
Regulation of the Hippo-YAP Pathway by G-Protein-Coupled Receptor Signaling
Yu, F.-X., Zhao, B., Panupinthu, N., Jewell, J. L., Lian, I., Wang, L. H., Zhao, J., Yuan, H., Tumaneng, K., Li, H., et al. (2012) · Cell · doi:10.1016/j.cell.2012.06.037 · Cited by 1,628
Metadata
- Authors
- Lee, K.-P., Lee, J.-H., Kim, T.-S., Kim, T.-H., Park, H.-D., Byun, J.-S., Kim, M.-C., Jeong, W.-I., Calvisi, D. F., Kim, J.-M., & Lim, D.-S.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2010-04-19
- Volume
- 107
- Issue
- 18
- Pages
- 8248-8253
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2067592231
- Cited by
- 493
- References
- 43
- FWCI
- 13.67
- Type
- journal article
- Language
- en
- Open access
- green
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- Lee, K.-P., Lee, J.-H., Kim, T.-S., Kim, T.-H., Park, H.-D., Byun, J.-S., Kim, M.-C., Jeong, W.-I., Calvisi, D. F., Kim, J.-M., & Lim, D.-S. (2010). The Hippo–Salvador pathway restrains hepatic oval cell proliferation, liver size, and liver tumorigenesis. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0912203107
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