title: Emerging roles for IL-11 signaling in cancer development and progression: Focus on breast cancer.
abstract: Interleukin (IL)-11 is a member of the IL-6 family of cytokines that is defined by the shared use of the GP130 signal transducing receptor subunit. In addition of its long recognized activities as a hemopoietic growth factor, IL-11 has an emerging role in epithelial cancer biology. Through the activation of the GP130-Janus kinase signaling cascade and associated transcription factor STAT3, IL-11 can confer many of the tumor intrinsic 'hallmark' capabilities to neoplastic cells, if they express the ligand-specific IL-11Rα receptor subunit. Accordingly, IL-11 signaling has recently been identified as a rate-limiting step for the growth tumors arising from the mucosa of the gastrointestinal tract. However, there is less appreciation for a potential role of IL-11 to support breast cancer progression, apart from its well documented capacity to facilitate bone metastasis. Here we review evidence that IL-11 expression in breast cancer correlates with poor disease outcome and discuss some of the molecular mechanisms that are likely to underpin these observations. These include the capacity of IL-11 to stimulate survival and proliferation of cancer cells alongside angiogenesis of the primary tumor and of metastatic progenies at distant organs. We review current strategies to interfere with IL-11 signaling and advocate that inhibition of IL-11 signaling may represent an emerging therapeutic opportunity for numerous cancers.
authors.affiliation: Cancer & Inflammation Laboratory, Olivia Newton-John Cancer Research Institute, Level 5, Olivia Newton-John Cancer & Wellness Centre, Heidelberg, VIC 3084, Australia; School of Cancer Medicine, LaTrobe University, Heidelberg, VIC 3084, Australia; Cancer Metastasis Laboratory, Cancer Research Division, Peter MacCallum Cancer Centre, East Melbourne, VIC 3002, Australia.
authors.forename: Cameron N
authors.initials: CN
authors.lastname: Johnstone
authors.affiliation: Cancer & Inflammation Laboratory, Olivia Newton-John Cancer Research Institute, Level 5, Olivia Newton-John Cancer & Wellness Centre, Heidelberg, VIC 3084, Australia; School of Cancer Medicine, LaTrobe University, Heidelberg, VIC 3084, Australia.
authors.forename: Ashwini
authors.initials: A
authors.lastname: Chand
authors.affiliation: Inflammation Division, Walter & Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, Melbourne University, Parkville, VIC 3052, Australia.
authors.forename: Tracy L
authors.initials: TL
authors.lastname: Putoczki
authors.affiliation: Cancer & Inflammation Laboratory, Olivia Newton-John Cancer Research Institute, Level 5, Olivia Newton-John Cancer & Wellness Centre, Heidelberg, VIC 3084, Australia; School of Cancer Medicine, LaTrobe University, Heidelberg, VIC 3084, Australia. Electronic address: matthias.ernst@onjcri.org.au.
authors.forename: Matthias
authors.initials: M
authors.lastname: Ernst
mesh_terms: D001943:Breast Neoplasms / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology*; D006801:Humans; D017370:Interleukin-11 / Q000276:immunology*; D009363:Neoplasm Proteins / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*
chemical_list: C508611:IL11 protein, human; D017370:Interleukin-11; D009363:Neoplasm Proteins
keywords: Cancer; IL-11; IL-6; Interleukin; STAT3