IL-6 and Stat3 are required for survival of intestinal epithelial cells and development of colitis-associated cancer

Cancer Cell. 2009 Feb 3;15(2):103-13. doi: 10.1016/j.ccr.2009.01.001.


Colitis-associated cancer (CAC) is the most serious complication of inflammatory bowel disease. Proinflammatory cytokines have been suggested to regulate preneoplastic growth during CAC tumorigenesis. Interleukin 6 (IL-6) is a multifunctional NF-kappaB-regulated cytokine that acts on epithelial and immune cells. Using genetic tools, we now demonstrate that IL-6 is a critical tumor promoter during early CAC tumorigenesis. In addition to enhancing proliferation of tumor-initiating cells, IL-6 produced by lamina propria myeloid cells protects normal and premalignant intestinal epithelial cells (IECs) from apoptosis. The proliferative and survival effects of IL-6 are largely mediated by the transcription factor Stat3, whose IEC-specific ablation has profound impact on CAC tumorigenesis. Thus, the NF-kappaB-IL-6-Stat3 cascade is an important regulator of the proliferation and survival of tumor-initiating IECs.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / physiology
  • Cell Proliferation
  • Cell Survival / physiology*
  • Colitis, Ulcerative / complications*
  • Colitis, Ulcerative / immunology
  • Colitis, Ulcerative / pathology
  • Epithelial Cells / cytology
  • Epithelial Cells / physiology*
  • Gene Expression Regulation
  • Humans
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism*
  • Intestinal Mucosa* / cytology
  • Intestinal Mucosa* / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • NF-kappa B / metabolism
  • Neoplasms* / etiology
  • Neoplasms* / immunology
  • Neoplasms* / pathology
  • STAT3 Transcription Factor / genetics
  • STAT3 Transcription Factor / metabolism*
  • Signal Transduction / physiology
  • Tumor Necrosis Factor-alpha / immunology


  • Interleukin-6
  • NF-kappa B
  • STAT3 Transcription Factor
  • Tumor Necrosis Factor-alpha