Enhanced expression of suppresser of cytokine signaling 3 inhibits the IL-6-induced epithelial-to-mesenchymal transition and cholangiocarcinoma cell metastasis

• Published in: Medical oncology (Northwood, London, England) London, England), 2015-04, Vol.32 (4), p.105-105, Article 105
• Main Authors: Zhou, Qing-Xin, Jiang, Xing-Ming, Wang, Zhi-Dong, Li, Chun-Long, Cui, Yun-Fu
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Bile Duct Neoplasms - metabolism; Bile Duct Neoplasms - pathology; Bile Duct Neoplasms - prevention & control; Bile Ducts, Intrahepatic - metabolism; Bile Ducts, Intrahepatic - pathology; Blotting, Western; Cell Movement; Cell Proliferation; Cholangiocarcinoma - metabolism; Cholangiocarcinoma - prevention & control; Cholangiocarcinoma - secondary; Epithelial-Mesenchymal Transition; Female; Fluorescent Antibody Technique; Gene Expression Regulation, Neoplastic; Hematology; Humans; Interleukin-6 - genetics; Interleukin-6 - metabolism; Internal Medicine; Medicine; Medicine & Public Health; Mice; Mice, Inbred BALB C; Mice, Nude; Oncology; Original Paper; Pathology; Phosphorylation; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; RNA, Small Interfering - genetics; Signal Transduction; Suppressor of Cytokine Signaling 3 Protein; Suppressor of Cytokine Signaling Proteins - antagonists & inhibitors; Suppressor of Cytokine Signaling Proteins - genetics; Suppressor of Cytokine Signaling Proteins - metabolism; Tumor Cells, Cultured; Wound Healing; Xenograft Model Antitumor Assays
• ISSN: 1357-0560; 1559-131X
• DOI: 10.1007/s12032-015-0553-7

It was recently demonstrated that interleukin-6 (IL-6) induces the epithelial-to-mesenchymal transition (EMT) in cholangiocarcinoma (CCA), but the underlying molecular mechanism remains to be explored. In this study, we studied the role of suppresser of cytokine signaling 3 (SOCS3), a negative feedback regulator of IL-6/STAT3, in the IL-6-induced EMT in CCA. Treatment with IL-6 induced the EMT by decreasing the E-cadherin expression and increasing the expression of N-cadherin and vimentin. Using wound healing and invasion assays, we found that IL-6 promoted cell motility. Further, a stably transfected cell line overexpressing SOCS3 was constructed. Enhanced SOCS3 expression decreased IL-6-induced cell invasion and EMT in parallel with downregulating the IL-6/STAT3 pathway. In contrast, SOCS3 silencing using siRNA exhibited no effect on the cell invasive ability and EMT. Finally, an in vivo study indicated that the enhancement of SOCS3 expression decreased metastasis compared with the control, and this effect was achieved by the repression of p-STAT3, N-cadherin and vimentin, and the induction of E-cadherin assessed by Western blot analysis. Our results suggest that enhanced expression of SOCS3 can antagonize IL-6-induced EMT and cell metastasis by abrogating the IL-6/STAT3 pathway. These data establish that SOCS3 plays a role in the EMT in CCA and may provide novel therapeutic strategies for CCA.