AI Article Synopsis
- Hippo signaling serves as a crucial tumor suppressor pathway by preventing the growth of adult stem and progenitor cells in several organs.
- Deletion of Hippo pathway components in the liver of mice leads to liver cancer by activating YAP and TAZ proteins, which are linked to many cancer types.
- The research indicates that the proteins WWC1 and NF2 work together to suppress cholangiocarcinoma by inhibiting the oncogenic activities of YAP/TAZ through LATS1/2 regulation.
Article Abstract
Hippo signaling acts as a tumor suppressor pathway by inhibiting the proliferation of adult stem cells and progenitor cells in various organs. Liver-specific deletion of Hippo pathway components in mice induces liver cancer development through activation of the transcriptional coactivators, YAP and TAZ, which exhibit nuclear enrichment and are activated in numerous types of cancer. The upstream-most regulators of Warts, the ortholog of mammalian LATS1/2, are Kibra, Expanded, and Merlin. However, the roles of the corresponding mammalian orthologs, WWC1, FRMD6 and NF2, in the regulation of LATS1/2 activity and liver tumorigenesis are not fully understood. Here, we show that deletion of both and in the liver accelerates intrahepatic cholangiocarcinoma (iCCA) development through activation of YAP/TAZ. Additionally, biliary epithelial cell-specific deletion of both and using a Sox9-Cre system resulted in iCCA development through hyperactivation of YAP/TAZ. These findings suggest that WWC1 and NF2 cooperate to promote suppression of cholangiocarcinoma development by inhibiting the oncogenic activity of YAP/TAZ via LATS1/2.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7264477 | PMC |
| http://dx.doi.org/10.14348/molcells.2020.0093 | DOI Listing |
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Article Synopsis
- Hippo signaling serves as a crucial tumor suppressor pathway by preventing the growth of adult stem and progenitor cells in several organs.
- Deletion of Hippo pathway components in the liver of mice leads to liver cancer by activating YAP and TAZ proteins, which are linked to many cancer types.
- The research indicates that the proteins WWC1 and NF2 work together to suppress cholangiocarcinoma by inhibiting the oncogenic activities of YAP/TAZ through LATS1/2 regulation.
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The Francis Crick Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK
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