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E2F1/SP3/STAT6 axis is required for IL-4-induced epithelial-mesenchymal transition of colorectal cancer cells

  • Authors:
    • Jiaoe Chen
    • Chaoju Gong
    • Huiqin Mao
    • Zhaoyun Li
    • Zejun Fang
    • Qiang Chen
    • Min Lin
    • Xiang Jiang
    • Yanyan Hu
    • Wei Wang
    • Xiaomin Zhang
    • Xianjun Chen
    • Hongzhang Li
  • View Affiliations / Copyright

    Affiliations: Department of Gastroenterology, Sanmen People's Hospital of Zhejiang, Sanmen, Zheijiang 317100, P.R. China, Xuzhou Key Laboratory of Ophthalmology, The First People's Hospital of Xuzhou, Xuzhou, Jiangsu 221002, P.R. China, Ultrasonography Department, Sanmen People's Hospital of Zhejiang, Sanmen, Zheijiang 317100, P.R. China, Clinical Laboratory, Taizhou Central Hospital, Taizhou University Hospital, Taizhou, Zheijiang 318000, P.R. China, Central Laboratory, Sanmen People's Hospital of Zhejiang, Sanmen, Zheijiang 317100, P.R. China, Pharmaceutical Preparation Section, Sanmen People's Hospital of Zhejiang, Sanmen, Zheijiang 317100, P.R. China
    Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 567-578
    |
    Published online on: June 5, 2018
       https://doi.org/10.3892/ijo.2018.4429
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Abstract

Colorectal cancer (CRC) is a type of cancer with a mortality rate among the highest worldwide owing to its high rate of metastasis. Therefore, inflammation-associated metastasis in the development of CRC is currently a topic of considerable interest. In the present study, the pro-inflammatory cytokine interleukin-4 (IL-4) was identified to promote the epithelial-mesenchymal transition (EMT) of CRC cells. However, the enhancing effect of IL-4 was more evident in HCT116 cells compared with in RKO cells. Accordingly, an increased expression level of STAT6 was observed in HCT116 cells compared with RKO cells. Further investigations identified that E2F1 was required for maintaining the level of signal transducer and activator of transcription 6 (STAT6) in HCT116 cells. Mechanistically, E2F1 induced specificity protein 3 (SP3) directly by binding to the promoter of the STAT6 gene and activating its transcription in CRC cells. As a result, phosphorylation-activated STAT6 increased the expression of several EMT drivers, including zinc finger E-box-binding homeobox (Zeb)1 and Zeb2, which serve a critical function in IL-4-induced EMT. Rescue experiments further confirmed that IL-4-induced EMT relied on an intact E2F1/SP3/STAT6 axis in CRC cells. Finally, analysis of clinical CRC specimens revealed a positive correlation between E2F1, SP3 and STAT6. The ectopically expressed E2F1/SP3/STAT6 axis indicated a poor prognosis in patients with CRC. In conclusion, the E2F1/SP3/STAT6 pathway was identified to be essential for IL-4 signaling-induced EMT and aggressiveness of CRC cells.
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Copy and paste a formatted citation
Spandidos Publications style
Chen J, Gong C, Mao H, Li Z, Fang Z, Chen Q, Lin M, Jiang X, Hu Y, Wang W, Wang W, et al: E2F1/SP3/STAT6 axis is required for IL-4-induced epithelial-mesenchymal transition of colorectal cancer cells. Int J Oncol 53: 567-578, 2018.
APA
Chen, J., Gong, C., Mao, H., Li, Z., Fang, Z., Chen, Q. ... Li, H. (2018). E2F1/SP3/STAT6 axis is required for IL-4-induced epithelial-mesenchymal transition of colorectal cancer cells. International Journal of Oncology, 53, 567-578. https://doi.org/10.3892/ijo.2018.4429
MLA
Chen, J., Gong, C., Mao, H., Li, Z., Fang, Z., Chen, Q., Lin, M., Jiang, X., Hu, Y., Wang, W., Zhang, X., Chen, X., Li, H."E2F1/SP3/STAT6 axis is required for IL-4-induced epithelial-mesenchymal transition of colorectal cancer cells". International Journal of Oncology 53.2 (2018): 567-578.
Chicago
Chen, J., Gong, C., Mao, H., Li, Z., Fang, Z., Chen, Q., Lin, M., Jiang, X., Hu, Y., Wang, W., Zhang, X., Chen, X., Li, H."E2F1/SP3/STAT6 axis is required for IL-4-induced epithelial-mesenchymal transition of colorectal cancer cells". International Journal of Oncology 53, no. 2 (2018): 567-578. https://doi.org/10.3892/ijo.2018.4429
Copy and paste a formatted citation
x
Spandidos Publications style
Chen J, Gong C, Mao H, Li Z, Fang Z, Chen Q, Lin M, Jiang X, Hu Y, Wang W, Wang W, et al: E2F1/SP3/STAT6 axis is required for IL-4-induced epithelial-mesenchymal transition of colorectal cancer cells. Int J Oncol 53: 567-578, 2018.
APA
Chen, J., Gong, C., Mao, H., Li, Z., Fang, Z., Chen, Q. ... Li, H. (2018). E2F1/SP3/STAT6 axis is required for IL-4-induced epithelial-mesenchymal transition of colorectal cancer cells. International Journal of Oncology, 53, 567-578. https://doi.org/10.3892/ijo.2018.4429
MLA
Chen, J., Gong, C., Mao, H., Li, Z., Fang, Z., Chen, Q., Lin, M., Jiang, X., Hu, Y., Wang, W., Zhang, X., Chen, X., Li, H."E2F1/SP3/STAT6 axis is required for IL-4-induced epithelial-mesenchymal transition of colorectal cancer cells". International Journal of Oncology 53.2 (2018): 567-578.
Chicago
Chen, J., Gong, C., Mao, H., Li, Z., Fang, Z., Chen, Q., Lin, M., Jiang, X., Hu, Y., Wang, W., Zhang, X., Chen, X., Li, H."E2F1/SP3/STAT6 axis is required for IL-4-induced epithelial-mesenchymal transition of colorectal cancer cells". International Journal of Oncology 53, no. 2 (2018): 567-578. https://doi.org/10.3892/ijo.2018.4429
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