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.
Bibliographical noteFunding Information:
This work was supported by the National Research Foundation of Korea (NRF) grant 2016R1A2B4013891 (awarded to S.W.R.), which was funded by the Korea government (MSIP)
All Science Journal Classification (ASJC) codes
- Molecular Biology