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: Cameron N Johnstone, Ashwini Chand, Tracy L Putoczki, Matthias Ernst
• Journal: Cytokine & growth factor reviews (Cytokine Growth Factor Rev) Vol. 26 Issue 5 Pg. 489-98 (Oct 2015) ISSN: 1879-0305 [Electronic] England
• PMID: 26209885 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Chemical References

• IL11 protein, human
• Interleukin-11
• Neoplasm Proteins

Topics

• Breast Neoplasms (immunology, mortality, pathology)
• Female
• Gene Expression Regulation, Neoplastic (immunology)
• Humans
• Interleukin-11 (immunology)
• Neoplasm Proteins (immunology)
• Signal Transduction (immunology)