Interleukin-11 is the dominant Il-6 family cytokine during gastrointestinal tumorigenesis and can be targeted therapeutically

Tracy L Putoczki, Stefan Thiem, Andrea Loving, Rita A Busuttil, Nicholas J. Wilson, Paul K. Ziegler, Paul M. Nguyen, Adele Preaudet, Ryan Farid, Kirsten M. Edwards, Yeliz Boglev, Rodney B. Luwor, Andrew Jarnicki, David Horst, Alex Boussioutas, Joan K. Heath, Oliver M Sieber, Irina Pleines, Benjamin T. Kile, Andrew NashFlorian R. Greten, Brent S McKenzie, Matthias Ernst

Research output: Contribution to journalArticleResearchpeer-review

248 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)257-271
Number of pages15
JournalCancer Cell
Volume24
Issue number2
DOIs
Publication statusPublished - 12 Aug 2013
Externally publishedYes

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