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

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dc.contributor.authorPutoczki, T.L.
dc.contributor.authorThiem, S.
dc.contributor.authorLoving, A.
dc.contributor.authorBusuttil, R.A.
dc.contributor.authorWilson, N.J.
dc.contributor.authorZiegler, P.K.
dc.contributor.authorNguyen, P.M.
dc.contributor.authorPreaudet, A.
dc.contributor.authorFarid, R.
dc.contributor.authorEdwards, K.M.
dc.contributor.authorBoglev, Y.
dc.contributor.authorLuwor, R.B.
dc.contributor.authorJarnicki, A.
dc.contributor.authorHorst, D.
dc.contributor.authorBoussioutas, A.
dc.contributor.authorHeath, J.K.
dc.contributor.authorSieber, O.M.
dc.contributor.authorPleines, I.
dc.contributor.authorKile, B.T.
dc.contributor.authorNash, A.
dc.contributor.authoret al.
dc.date.issued2013
dc.description.abstractAmong 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.
dc.description.statementofresponsibilityTracy L.Putoczki, Stefan Thiem, Andrea Loving, Rita A.Busuttil, Nicholas J.Wilson ... Benjamin T. Kile ... et al.
dc.identifier.citationCancer Cell, 2013; 24(2):257-271
dc.identifier.doi10.1016/j.ccr.2013.06.017
dc.identifier.issn1535-6108
dc.identifier.issn1878-3686
dc.identifier.orcidKile, B.T. [0000-0002-8836-8947]
dc.identifier.urihttp://hdl.handle.net/2440/121742
dc.language.isoen
dc.publisherCell Press
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1008614
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/487922
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1016647
dc.rights© 2013 Elsevier Inc.
dc.source.urihttps://doi.org/10.1016/j.ccr.2013.06.017
dc.subjectMolecular Targeted Therapy
dc.titleInterleukin-11 is the dominant Il-6 family cytokine during gastrointestinal tumorigenesis and can be targeted therapeutically
dc.typeJournal article
pubs.publication-statusPublished

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