Interleukin-11-expressing fibroblasts have a unique gene signature correlated with poor prognosis of colorectal cancer
Open Access
- 16 April 2021
- journal article
- research article
- Published by Springer Nature in Nature Communications
- Vol. 12 (1) , 1-20
Abstract
Interleukin (IL)-11 is a member of the IL-6 family of cytokines and is involved in multiple cellular responses, including tumor development. However, the origin and functions of IL-11-producing (IL-11+) cells are not fully understood. To characterize IL-11+cells in vivo, we generateIl11reporter mice. IL-11+cells appear in the colon in murine tumor and acute colitis models.Il11ra1orIl11deletion attenuates the development of colitis-associated colorectal cancer. IL-11+cells express fibroblast markers and genes associated with cell proliferation and tissue repair. IL-11 induces the activation of colonic fibroblasts and epithelial cells through phosphorylation of STAT3. Human cancer database analysis reveals that the expression of genes enriched in IL-11+fibroblasts is elevated in human colorectal cancer and correlated with reduced recurrence-free survival. IL-11+fibroblasts activate both tumor cells and fibroblasts via secretion of IL-11, thereby constituting a feed-forward loop between tumor cells and fibroblasts in the tumor microenvironment.Keywords
This publication has 55 references indexed in Scilit:
- Interleukin-11 Is the Dominant IL-6 Family Cytokine during Gastrointestinal Tumorigenesis and Can Be Targeted TherapeuticallyCancer Cell, 2013
- TCC: an R package for comparing tag count data with robust normalization strategiesBMC Bioinformatics, 2013
- Dependency of Colorectal Cancer on a TGF-β-Driven Program in Stromal Cells for Metastasis InitiationCancer Cell, 2012
- Fast gapped-read alignment with Bowtie 2Nature Methods, 2012
- Interleukin-11 Links Oxidative Stress and Compensatory ProliferationScience Signaling, 2012
- Non-core Region Modulates Interleukin-11 Signaling ActivityJournal of Biological Chemistry, 2011
- edgeR: a Bioconductor package for differential expression analysis of digital gene expression dataBioinformatics, 2009
- STAT3 links IL-22 signaling in intestinal epithelial cells to mucosal wound healingJournal of Experimental Medicine, 2009
- Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profilesProceedings of the National Academy of Sciences, 2005
- PGC-1α-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetesNature Genetics, 2003