Interleukin-11 Is the Dominant IL-6 Family Cytokine during Gastrointestinal Tumorigenesis and Can Be Targeted Therapeutically
Details
Publication Year 2013-08-12, Volume 24, Issue #2, Page 257-271
Journal Title
CANCER CELL
Publication Type
Journal Article
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.
Publisher
CELL PRESS
Keywords
CHRONIC LYMPHOCYTIC-LEUKEMIA; SURVIVAL SIGNALS; CELL-DEATH; THERAPY; FAMILY; INHIBITOR; TUMORS; NAVITOCLAX; ABT-737; ACTIVATIO
WEHI Research Division(s)
Cancer And Haematology; Systems Biology And Personalised Medicine; Chemical Biology; Bioinformatics; Stem Cells And Cancer; Molecular Medicine
NHMRC Grants
NHMRC/487922 NHMRC/1016647
Rights Notice
Copyright © 2013 Elsevier Inc. All rights reserved.


Creation Date: 2013-08-12 12:00:00
Last Modified: 0001-01-01 12:00:00
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