Original ResearchFull Report: Basic and Translational—LiverActivation of β-Catenin and Yap1 in Human Hepatoblastoma and Induction of Hepatocarcinogenesis in Mice
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Human HB, HCC, and ICC Samples
Ninety-four HB samples collected at the University of Basel (Switzerland), University of Greifswald (Germany), University of Tuebingen (Germany), and University of Pittsburgh (United States) were assessed for Yap and β-catenin expression by immunohistochemistry (Supplementary Table 1). A recently described collection of 103 HCC specimens from Europe (Supplementary Table 2)14 and a collection of 62 ICC samples from the University of Basel and University of Greifswald were also assessed for Yap
Concurrent Nuclear Localization of YAP and β-Catenin Is Evident in Human HB but not HCC or ICC Specimens
To investigate any possible cooperation between Yap and β-catenin pathways in human liver tumors, first we evaluated the activation of the 2 cascades in a large collection of human HCC, ICC, and HB specimens. Nuclear accumulation of β-catenin and Yap proteins via immunohistochemistry is indicative of activation of respective pathways. In HCC samples (n = 103), 28% of HCC cases showed nuclear β-catenin immunoreactivity, whereas nuclear Yap was observed in 65% of tumors (Table 1 and Figure 1).
Discussion
HB is the most common primary malignant neoplasm of the liver in childhood.1 The cellular and molecular basis of the disease is poorly understood. Aberrant Wnt/β-catenin signaling has long been considered a hallmark of HB, with a rate of point mutations and genetic deletions in the β-catenin gene evident in almost 90% of cases. However, overexpression of oncogenic forms of β-catenin has never led to HB in mice, which has strongly suggested its cooperation with another pathway in the
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Conflicts of interest The authors disclose no conflicts.
Funding Supported by grants 1R01DK62277, 1R01DK100287 and Endowed Chair for Experimental Pathology (to S.P.S.M.) and 1R01CA136606 and UCSF Liver Center (to X.C.) and in part by grant EV 168/2-1 (to M.E.).
Author names in bold designate shared co-first authorship.
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Authors share co-first authorship.