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Pro-tumorigenic roles of TGF-モ signaling during the early stages of liver tumorigenesis through upregulation of Snail
Hyuk Moon1, Kwang-Hyub Han1, Simon Weonsang Ro1,*
1Institute of Gastroenterology and 2Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722 South Korea
Many studies have focused on the tumor suppressive role of TGF-モ signaling during the early stages of tumorigenesis by activating the target genes involved in cytostasis and apoptosis. We investigated the effects of TGF-モ inhibition on early tumorigenesis in the liver, by employing diverse inhibitory methods. Strikingly, TGF-モ 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-モ signaling in tumorigenesis. Moreover, we found that Snail is the target gene of the TGF-モ signaling pathway that promotes hepatic carcinogenesis. The knockdown of Snail suppressed the early tumorigenesis in the liver, as did the TGF-モ inhibition, while the ectopic expression of Snail restored tumorigenesis that was suppressed by the TGF-モ inhibition. Our findings establish the oncogenic TGF-モ-Smad-Snail signaling axis during the early tumorigenesis in the liver.
Abstract, Accepted Manuscript [Submitted on October 23, 2017, Accepted on October 23, 2017]
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