Putoczki, T.L.Thiem, S.Loving, A.Busuttil, R.A.Wilson, N.J.Ziegler, P.K.Nguyen, P.M.Preaudet, A.Farid, R.Edwards, K.M.Boglev, Y.Luwor, R.B.Jarnicki, A.Horst, D.Boussioutas, A.Heath, J.K.Sieber, O.M.Pleines, I.Kile, B.T.Nash, A.et al.2019-10-302019-10-302013Cancer Cell, 2013; 24(2):257-2711535-61081878-3686http://hdl.handle.net/2440/121742Among 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.en© 2013 Elsevier Inc.Molecular Targeted TherapyJournal article100000187910.1016/j.ccr.2013.06.0170003231412000132-s2.0-84881534116500259Kile, B.T. [0000-0002-8836-8947]