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. Author manuscript; available in PMC: 2013 Jul 2.
Published in final edited form as: Physiol Rev. 2012 Oct;92(4):1515–1542. doi: 10.1152/physrev.00047.2011

FIGURE 8.

FIGURE 8

Signaling pathways leading to HCC in Gnmt KO mice. Loss of GNMT activity induces an abnormal accumulation of hepatic AdoMet leading to a major epigenetic alteration in gene expression regulation. These epigenetic changes include the hypermethylation of Rassf1 and Socs2 promoters, as well as the trimethylation of histone 3 lysine 27 associated with these genes. As a consequence, the expression of Rassf1 and Socs2, as well as of other inhibitors of Ras and JAK/STAT signaling pathways, is downregulated. This leads to the activation of Ras and JAK/STAT signaling pathways, to abnormal growth, and to malignant transformation.