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;
Publication Year 2013-08-12, Volume 24, Issue #2, Page 257-271
- Journal Title
- CANCER CELL
- Publication Type
- Journal Article
- 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
- WEHI Research Division(s)
- Cancer And Haematology; Systems Biology And Personalised Medicine; Chemical Biology; Bioinformatics; Stem Cells And Cancer; Molecular Medicine
- Publisher's Version
- Rights Notice
- Copyright © 2013 Elsevier Inc. All rights reserved.
Creation Date: 2013-08-12 12:00:00Last Modified: 0001-01-01 12:00:00