Astrocyte elevated gene-1 regulates hepatocellular carcinoma development and progression

摘要: Hepatocellular carcinoma (HCC) is a highly aggressive vascular cancer characterized by diverse etiology, activation of multiple signal transduction pathways, and various gene mutations. Here, we have determined specific role for astrocyte elevated gene-1 (AEG1) in HCC pathogenesis. Expression AEG1 was extremely low human hepatocytes, but its levels were significantly increased HCC. Stable overexpression converted nontumorigenic cells into tumors, inhibition abrogated tumorigenesis xenograft model nude mice. In HCC, associated with copy numbers. Microarray analysis revealed that modulated the expression genes invasion, metastasis, chemoresistance, angiogenesis, senescence. also found to activate Wnt/β-catenin signaling via ERK42/44 upregulated lymphoid-enhancing factor 1/T cell 1 (LEF1/TCF1), ultimate executor Wnt pathway, important progression. Inhibition studies further demonstrated played key mediating function. activated NF-κB which may play chronic inflammatory changes preceding development. These data indicate plays central regulating aspects Targeted might lead shutdown elemental characteristics could an effective therapeutic strategy