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

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Abstract

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.

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Acknowledgments

This study was supported by the National Natural Science Foundation of China (No. 81170426).

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical standard

All applicable international, national and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the study were conducted. This article does not contain any studies with human participants performed by any of the authors.

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Informed consent was obtained from all individual participants included in the study.

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Authors and Affiliations

  1. Department of Hepato-Biliary-Pancreatic Surgery, The Second Affiliated Hospital, Harbin Medical University, No. 246 Xuefu Road, Harbin, 150086, Heilongjiang Province, China

    Qing-Xin Zhou, Xing-Ming Jiang, Zhi-Dong Wang, Chun-Long Li & Yun-Fu Cui

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  1. Qing-Xin Zhou
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  2. Xing-Ming Jiang
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Correspondence to Yun-Fu Cui.

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Zhou, QX., Jiang, XM., Wang, ZD. et al. Enhanced expression of suppresser of cytokine signaling 3 inhibits the IL-6-induced epithelial-to-mesenchymal transition and cholangiocarcinoma cell metastasis. Med Oncol 32, 105 (2015). https://doi.org/10.1007/s12032-015-0553-7

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