STAT3 aggravates TGF- β1-induced hepatic epithelial-to-mesenchymal transition and migration

Publication date: February 2018 Source:Biomedicine & Pharmacotherapy, Volume 98 Author(s): Bin Wang, Ting Liu, Jun-Cheng Wu, Sheng-Zheng Luo, Rong Chen, Lun-Gen Lu, Ming-Yi Xu Signal transducer and activator of transcription 3 (STAT3) has been shown to affect epithelial-to-mesenchymal transition (EMT) in cancers. We investigated the underlying molecular mechanisms of STAT3 crosstalk with Snail-Smad3/transforming growth factor (TGF)-β1 signaling pathways during the EMT in hepatocellular carcinoma (HCC). STAT3 and TGF-β1 expressions are examined in liver tissues of HCC patients and rats. The effect of IL-6/ STAT3 crosstalk with Snail-Smad3/TGF-β1 on EMT, carcinogenesis, migration and invasion are tested in vitro and in vivo. Phosphorylation of STAT3 and TGF-β1 proteins are universally high and positively co-expressed in HCC tissues from human and rats. Hepatic lower p-STAT3 proteins are related to earlier tumor stages in HCC patients. AG490 (a JAK2-specific inhibitor) treatment could reduce tumor numbers and sizes depending on suppression of STAT3 signaling in HCC rats. TGF-β1 could induce EMT along with an E-cadherin decrease, while vimentin, Snail, p-Smad2/3, and p-STAT3/STAT3 increase in HepG2. SIS3 (a specific inhibitor of Smad3) could markedly inhibit Snail, Vim and p-STAT3 along with blocking phosphorylation of Smad3, but E-cadherin could be activated in HepG2. IL-6 activates STAT3 signaling and then has cascading consequences for activating Snail-Sm...
Source: Biomedicine and Pharmacotherapy - Category: Drugs & Pharmacology Source Type: research