Cancer Cell
Volume 24, Issue 2, 12 August 2013, Pages 257-271
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Article
Interleukin-11 Is the Dominant IL-6 Family Cytokine during Gastrointestinal Tumorigenesis and Can Be Targeted Therapeutically

https://doi.org/10.1016/j.ccr.2013.06.017Get rights and content
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Highlights

  • Elevated IL-11 levels in GI tumors correlate with oncogenic STAT3 activation

  • IL-11 is the dominant IL-6 family cytokine required for GI cancer progression

  • IL-11/STAT3 signaling promotes tumor cell proliferation and survival

  • Therapeutic inhibition of IL-11 signaling impedes GI tumorigenesis in vivo

Summary

Among the cytokines linked to inflammation-associated cancer, interleukin (IL)-6 drives many of the cancer “hallmarks” through downstream activation of the gp130/STAT3 signaling pathway. However, we show that the related cytokine IL-11 has a stronger correlation with elevated STAT3 activation in human gastrointestinal cancers. Using genetic mouse models, we reveal that IL-11 has a more prominent role compared to IL-6 during the progression of sporadic and inflammation-associated colon and gastric cancers. Accordingly, in these models and in human tumor cell line xenograft models, pharmacologic inhibition of IL-11 signaling alleviated STAT3 activation, suppressed tumor cell proliferation, and reduced the invasive capacity and growth of tumors. Our results identify IL-11 signaling as a potential therapeutic target for the treatment of gastrointestinal cancers.

Cited by (0)

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Present address: Department of Medical Biology, The University of Melbourne, VIC 3050, Australia

11

Present address: Walter and Eliza Hall Institute of Medical Research, VIC 3052, Australia

12

Present address: School of Biomedical Sciences and Pharmacy, University of Newcastle, NSW 2308, Australia