Interleukin-6 stimulates aerobic glycolysis by regulating PFKFB3 at early stage of colorectal cancer

  • Authors:
    • Jun Han
    • Qingyang Meng
    • Qiulei Xi
    • Yongxian Zhang
    • Qiulin Zhuang
    • Yusong Han
    • Yi Jiang
    • Qiurong Ding
    • Guohao Wu
  • View Affiliations

  • Published online on: November 2, 2015     https://doi.org/10.3892/ijo.2015.3225
  • Pages: 215-224
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Abstract

Chronic inflammation is a well-known etiological factor for colorectal cancer (CRC) and cancer cells are known to preferentially metabolize glucose through aerobic glycolysis. However, the connection between chronic inflammation and aerobic glycolysis in the development of CRC is largely unexplored. The present study investigated whether interleukin-6 (IL-6), a pro-inflammatory cytokine, promotes the development of CRC by regulating the aerobic glycolysis and the underlying molecular mechanisms. In colitis-associated CRC mouse, anti-IL-6 receptor antibody treatment reduced the incidence of CRC and decreased the expression of key genes in aerobic glycolysis, whereas the plasma concentrations of glucose and lactate were not affected. Consistently, IL-6 treatment stimulated aerobic glycolysis, upregulated key genes in aerobic glycolysis and promoted cell proliferation and migration in SW480 and SW1116 CRC cells. 6-phoshofructo-2-kinase/fructose-2,6-bisphosphatase-3 (PFKFB3) was the most downregulated gene by anti-IL-6 receptor antibody in colorectal adenoma tissues. Further analysis in human samples revealed overexpression of PFKFB3 in colorectal adenoma and adenocarcinoma tissues, which was also associated with lymph node metastasis, intravascular cancer embolus and TNM stage. In addition, the effect of IL-6 on CRC cells can be abolished by knocking down PRKFB3 through siRNA transfection. Our data suggest that chronic inflammation promotes the development of CRC by stimulating aerobic glycolysis and IL-6 is functioning, at least partly, through regulating PFKFB3 at early stage of CRC.
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January-2016
Volume 48 Issue 1

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Spandidos Publications style
Han J, Meng Q, Xi Q, Zhang Y, Zhuang Q, Han Y, Jiang Y, Ding Q and Wu G: Interleukin-6 stimulates aerobic glycolysis by regulating PFKFB3 at early stage of colorectal cancer. Int J Oncol 48: 215-224, 2016
APA
Han, J., Meng, Q., Xi, Q., Zhang, Y., Zhuang, Q., Han, Y. ... Wu, G. (2016). Interleukin-6 stimulates aerobic glycolysis by regulating PFKFB3 at early stage of colorectal cancer. International Journal of Oncology, 48, 215-224. https://doi.org/10.3892/ijo.2015.3225
MLA
Han, J., Meng, Q., Xi, Q., Zhang, Y., Zhuang, Q., Han, Y., Jiang, Y., Ding, Q., Wu, G."Interleukin-6 stimulates aerobic glycolysis by regulating PFKFB3 at early stage of colorectal cancer". International Journal of Oncology 48.1 (2016): 215-224.
Chicago
Han, J., Meng, Q., Xi, Q., Zhang, Y., Zhuang, Q., Han, Y., Jiang, Y., Ding, Q., Wu, G."Interleukin-6 stimulates aerobic glycolysis by regulating PFKFB3 at early stage of colorectal cancer". International Journal of Oncology 48, no. 1 (2016): 215-224. https://doi.org/10.3892/ijo.2015.3225