Therapeutically exploiting STAT3 activity in cancer — using tissue repair as a road map
Top Cited Papers
- 21 December 2018
- journal article
- review article
- Published by Springer Science and Business Media LLC in Nature Reviews Cancer
- Vol. 19 (2), 82-96
- https://doi.org/10.1038/s41568-018-0090-8
Abstract
The tightly orchestrated temporal and spatial control of signal transducer and activator of transcription 3 (STAT3) activity in epithelial, immune and stromal cells is critical for wound healing and tissue repair. Excessive STAT3 activation within cancer cells and cells of the tumour microenvironment can be viewed as a neoplastic mimic of an inflammation-driven repair response that collectively promotes tumour progression. In addition to the canonical transcriptional pathways by which STAT3 promotes stem cell-like characteristics, survival, proliferation, metastatic potential and immune evasion, cytoplasmic STAT3 activity fuels tumour growth by metabolic and other non-transcriptional mechanisms. Here, we review the tumour-modulating activities of STAT3 in light of its role as a signalling node integrating inflammatory responses during wound healing. Accordingly, many of the cytokines that contribute to the para-inflammatory state of most solid malignancies converge on and underpin dysregulated STAT3 activity. Targeting of these cytokines, their cognate receptors and associated signalling cascades in clinical trials is beginning to demonstrate therapeutic efficacy, given that interference with STAT3 activity is likely to simultaneously curb the growth of cancer cells and augment antitumour immunity.Keywords
This publication has 198 references indexed in Scilit:
- STAT3 activity is necessary and sufficient for the development of immune‐mediated myocarditis in mice and promotes progression to dilated cardiomyopathyEMBO Molecular Medicine, 2013
- Cytoplasmic STAT3 Represses Autophagy by Inhibiting PKR ActivityMolecular Cell, 2012
- Dependency of Colorectal Cancer on a TGF-β-Driven Program in Stromal Cells for Metastasis InitiationCancer Cell, 2012
- Genetic partitioning of interleukin‐6 signalling in mice dissociates Stat3 from Smad3‐mediated lung fibrosisEMBO Molecular Medicine, 2012
- Hallmarks of Cancer: The Next GenerationCell, 2011
- STAT3-induced S1PR1 expression is crucial for persistent STAT3 activation in tumorsNature Medicine, 2010
- Teaching old receptors new tricks: biasing seven-transmembrane receptorsNature Reviews Drug Discovery, 2010
- STAT3 inhibition of gluconeogenesis is downregulated by SirT1Nature, 2009
- Regulation of the IL-23 and IL-12 Balance by Stat3 Signaling in the Tumor MicroenvironmentCancer Cell, 2009
- Mechanisms and functional significance of tumour-induced dendritic-cell defectsNature Reviews Immunology, 2004