PUBLICATION
cGAMP inhibits tumor growth in colorectal cancer metastasis through the STING/STAT3 axis in a zebrafish xenograft model
- Authors
- Jiang, X., Liu, G., Hu, Z., Chen, G., Chen, J., Lv, Z.
- ID
- ZDB-PUB-191006-3
- Date
- 2019
- Source
- Fish & shellfish immunology 95: 220-226 (Journal)
- Registered Authors
- Keywords
- Colorectal cancer, Metastasis, STING/STAT3 axis, cGAMP
- MeSH Terms
-
- Animals
- Antineoplastic Agents/pharmacology*
- Colorectal Neoplasms/pathology
- Colorectal Neoplasms/veterinary*
- Disease Models, Animal
- Heterografts/pathology*
- Liver Neoplasms/secondary
- Liver Neoplasms/veterinary*
- Membrane Proteins/genetics
- Neoplasm Metastasis
- Nucleotides, Cyclic/pharmacology*
- STAT3 Transcription Factor/genetics
- Signal Transduction*
- Zebrafish
- Zebrafish Proteins/genetics
- PubMed
- 31586458 Full text @ Fish Shellfish Immunol.
Citation
Jiang, X., Liu, G., Hu, Z., Chen, G., Chen, J., Lv, Z. (2019) cGAMP inhibits tumor growth in colorectal cancer metastasis through the STING/STAT3 axis in a zebrafish xenograft model. Fish & shellfish immunology. 95:220-226.
Abstract
The leading cause of mortality due to colorectal cancer (CRC) is highly associated with the development of liver metastases. Recently, we described cGAMP that is closely related to the metastatic state wherein the progress of metastatic tumors is associated with favorable outcomes in a zebrafish xenograft model. cGAMP was administered and the expression levels of type-I interferons were induced amongst tumor tissues to illuminate the overall measure of the induced STING/STAT3 axis in colorectal liver metastases. Furthermore, cGAMP-STING dependent STAT3 activation resulted in the inhibition of tumor cell proliferation, viability, and invasion in vitro. The subtotal reduction in tumor growth attributed to a large number of infiltrating inflammatory cells in vivo. We showed that cGAMP inhibited migration through angiogenesis by up-regulating IL-2, TNF-α, and IFN-γ, whereas STAT3 down-regulation inhibited CXCL8, BCL-2, and VEGFA expression. The importance of cGAMP in inhibiting the invasion front of CRC confirmed that the cGAMP dependent activation of STING/STAT3 axis played a key role in the inhibition of tumor progression.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping