Mst1 and Mst2 Maintain Hepatocyte Quiescence and Suppress Hepatocellular Carcinoma Development through Inactivation of the Yap1 Oncogene

View/ Open
Author
Zhou, Dawang
Park, Ji-Sun
Yin, Yi
Thasler, Wolfgang
Bardeesy, Nabeel
Note: Order does not necessarily reflect citation order of authors.
Published Version
https://doi.org/10.1016/j.ccr.2009.09.026Metadata
Show full item recordCitation
Zhou, Dawang, Claudius Conrad, Fan Xia, Ji-Sun Park, Bernhard Payer, Yi Yin, Gregory Y. Lauwers, et al. 2009. Mst1 and Mst2 maintain hepatocyte quiescence and suppress hepatocellular carcinoma development through inactivation of the Yap1 oncogene. Cancer Cell 16(5): 425–438. doi:10.1016/j.ccr.2009.09.026Abstract
Hippo-Lats-Yorkie signaling regulates tissue overgrowth and tumorigenesis in Drosophila. We show that the Mst1 and Mst2 protein kinases, the mammalian Hippo orthologs, are cleaved and constitutively activated in the mouse liver. Combined Mst1/2 deficiency in the liver results in loss of inhibitory Ser127 phosphorylation of the Yorkie ortholog, Yap1, massive overgrowth, and hepatocellular carcinoma (HCC). Reexpression of Mst1 in HCC-derived cell lines promotes Yap1 Ser127 phosphorylation and inactivation and abrogates their tumorigenicity. Notably, Mst1/2 inactivates Yap1 in liver through an intermediary kinase distinct from Lats1/2. Approximately 30% of human HCCs show low Yap1(Ser127) phosphorylation and a majority exhibit loss of cleaved, activated Mst1. Mst1/2 inhibition of Yap1 is an important pathway for tumor suppression in liver relevant to human HCC.Other Sources
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3023165/Terms of Use
This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAACitable link to this page
http://nrs.harvard.edu/urn-3:HUL.InstRepos:32540912
Collections
- HMS Scholarly Articles [17875]
Contact administrator regarding this item (to report mistakes or request changes)