Methylation silencing of SOCS-3 promotes cell growth and migration by enhancing JAK/STAT and FAK signalings in human hepatocellular carcinoma
作者： Yasuharu Niwa , Hiroaki Kanda , Yuko Shikauchi , Akio Saiura , Kenichi Matsubara
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摘要: We identified that suppressor of cytokine signaling-3 (SOCS-3) gene was aberrantly methylated in its CpG island three 10 human hepatocellular carcinoma (HCC) cell lines. SOCS-3 RNA undetectable five the HCC lines including lines, and a demethylating agent, 5-aza-2'-deoxycytidine, reactivated expression tested. The DNA region where we found aberrant methylation includes signal transducers activators transcription (STAT) binding consensus sequence. When used as promoter, markedly reduced promoter activity. also six 18 primary samples. one unmethylated samples examined. Restoration cells lacking suppressed STAT3 phosphorylation growth. IL-6 acted growth factor cells. Inhibition whose induced by enhanced In addition, AG490, chemical JAK2 inhibitor, downregulated phosphorylation, but not FAK phosphorylation. physically interacted with phosphorylated Elongin B decreased well protein level. increased resulting enhancement migration. These data indicate negatively regulates motility inhibiting Janus kinase (JAK)/STAT signalings Thus, loss associated confers advantage
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