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KMID : 0624620170500120599
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BMB Reports
2017 Volume.50 No. 12 p.599 ~ p.600
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Pro-tumorigenic roles of TGF-β signaling during the early stages of liver tumorigenesis through upregulation of Snail
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Moon Hyuk
Han Kwang-Hyub
Ro Simon Weon-Sang
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Abstract
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Many studies have focused on the tumor suppressive role of TGF-β signaling during the early stages of tumorigenesis by activating the target genes involved in cytostasis and apoptosis. We investigated the effects of TGF-β inhibition on early tumorigenesis in the liver, by employing diverse inhibitory methods. Strikingly, TGF-β inhibition consistently suppressed hepatic tumorigenesis that was induced either by activated RAS plus p53 downregulation or by the co-activation of RAS and TAZ signaling; this demonstrates the requirements for canonical TGF-β signaling in tumorigenesis. Moreover, we found that Snail is the target gene of the TGF-β signaling pathway that promotes hepatic carcinogenesis. The knockdown of Snail suppressed the early tumorigenesis in the liver, as did the TGF-β inhibition, while the ectopic expression of Snail restored tumorigenesis that was suppressed by the TGF-β inhibition. Our findings establish the oncogenic TGF-β-Smad-Snail signaling axis during the early tumorigenesis in the liver.
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KEYWORD
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Cancer model, Hepatocellular carcinoma, Snail, Transforming growth factor β (TGF-β), Tumor promotion
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