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- W2125156743 abstract "The molecular signals that control the maintenance and activation of liver stem/progenitor cells are poorly understood, and the role of liver progenitor cells in hepatic tumorigenesis is unclear. We report here that liver-specific deletion of the neurofibromatosis type 2 ( Nf2 ) tumor suppressor gene in the developing or adult mouse specifically yields a dramatic, progressive expansion of progenitor cells throughout the liver without affecting differentiated hepatocytes. All surviving mice eventually developed both cholangiocellular and hepatocellular carcinoma, suggesting that Nf2 −/− progenitors can be a cell of origin for these tumors. Despite the suggested link between Nf2 and the Hpo/Wts/Yki signaling pathway in Drosophila , and recent studies linking the corresponding Mst/Lats/Yap pathway to mammalian liver tumorigenesis, our molecular studies suggest that Merlin is not a major regulator of YAP in liver progenitors, and that the overproliferation of Nf2 −/− liver progenitors is instead driven by aberrant epidermal growth factor receptor (EGFR) activity. Indeed, pharmacologic inhibition of EGFR blocks the proliferation of Nf2 −/− liver progenitors in vitro and in vivo, consistent with recent studies indicating that the Nf2 -encoded protein Merlin can control the abundance and signaling of membrane receptors such as EGFR. Together, our findings uncover a critical role for Nf2/Merlin in controlling homeostasis of the liver stem cell niche." @default.
- W2125156743 created "2016-06-24" @default.
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- W2125156743 creator A5065925695 @default.
- W2125156743 date "2010-07-30" @default.
- W2125156743 modified "2023-09-30" @default.
- W2125156743 title "<i>Nf2</i>/Merlin controls progenitor homeostasis and tumorigenesis in the liver" @default.
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- W2125156743 doi "https://doi.org/10.1101/gad.1938710" @default.
- W2125156743 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2922501" @default.
- W2125156743 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/20675406" @default.
- W2125156743 hasPublicationYear "2010" @default.
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