STAT3 aggravates TGF-β1 induced epithelial-to-mesenchymal transition  in hepatocellular carcinoma cells

Abstract

Abstract: Objective To investigate the underlying molecular mechanisms of interleukin-6/Janus kinase/ signal transducer and activator of transcription (IL-6/JAK/STAT3) and Smad3/transforming growth factor-β1 (Smad3/TGF-β1) signaling pathways during the epithelial to mesenchymal transition (EMT) process in hepatocellular carcinoma (HCC) cells.Methods Human HCC cell lines HepG2 and HCCLM3 were treated with TGF-β1, AG490 and IL-6, respectively. mRNA expressions of STAT3 and Snail were measured using quantitative PCR. Expressions of p-STAT3/STAT3, p-Smad3/Smad3, TGF-β1 and EMT-related markers were measured using western blotting. Results TGF-β1 induced EMT in HepG2 cells, dampen E-Cadherin expression and up-regulate expressions of vimentin, Snail, p-Smad2/3 and p-STAT3/STAT3. IL-6 activated Smad3/TGF-β1 pathway by stimulating STAT3 in human HCC lines, and up-regulated expressions of EMT-related molecular markers (Snail and Vimentin). AG490, the JAK2-specific inhibitor, inhibited expressions of p-STAT3/STAT3, p-Smad3 and Snail.Conclusion STAT3 aggravated TGF-β1-induced EMT and HCC metastasis, which performed a synergistical effect with IL-6/JAK/STAT3 and Snail/Smad3/TGF-β1 signaling pathways.

Key words: Hepatocellular carcinoma, Epithelial-to-mesenchymal transition, Signal transducer and activator of transcription 3, Transforming growth factor-β1

LIU Ting, WU Jun-cheng, LU Lun-gen, XU Ming-yi.. STAT3 aggravates TGF-β1 induced epithelial-to-mesenchymal transition in hepatocellular carcinoma cells[J]. Chinese Hepatolgy, 2018, 23(2): 128-132.

References

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STAT3 aggravates TGF-β1 induced epithelial-to-mesenchymal transition in hepatocellular carcinoma cells

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