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Interleukin-11 Is the Dominant IL-6 Family Cytokine during Gastrointestinal Tumorigenesis and Can Be Targeted Therapeutically


Putoczki, TL; Thiem, S; Loving, A; Busutti, RA; Wilson, NJ; Ziegler, PK; Nguyen, PM; Preaudet, A; Farid, R; Edwards, KM; Boglev, Y; Luwor, RB; Jarnicki, A; Horst, D; Boussioutas, A; Heath, JK; Sieber, OM; Pleines, I; Kile, BT; Nash, A; Greten, FR; McKenzie, BS; Ernst, M
2013-08-12
CANCER CELL
Journal Article
24
2
257-271
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.
CELL PRESS
CHRONIC LYMPHOCYTIC-LEUKEMIA; SURVIVAL SIGNALS; CELL-DEATH; THERAPY; FAMILY; INHIBITOR; TUMORS; NAVITOCLAX; ABT-737; ACTIVATIO
Stem Cells and Cancer; Molecular Medicine; Bioinformatics; Chemical Biology; Systems Biology and Personalised Medicine; Cancer and Haematology
10.1016/j.ccr.2013.06.017
Refer to article for additional funding acknowledgements
Copyright © 2013 Elsevier Inc. All rights reserved.

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Creation Date 2013-08-12 12:00:00