Back to Search
Start Over
Periostin–TGF-β feedforward loop contributes to tumour-stroma crosstalk in liver metastatic outgrowth of colorectal cancer.
- Source :
-
British Journal of Cancer . Feb2024, Vol. 130 Issue 3, p358-368. 11p. - Publication Year :
- 2024
-
Abstract
- Background: This study aimed to investigate the underlying mechanisms of matricellular protein periostin (POSTN) on tumour-stroma crosstalk in the liver metastatic microenvironment of colorectal cancer (CRC). Methods: Postn-knockout mice and hepatic Postn-overexpressing mice were used to investigate the functions of POSTN on the formation of fibrotic microenvironment and the tumour-stroma crosstalk in the liver metastatic microenvironment of CRC. Clinical samples and database were analyzed to show the correlation between POSTN expression and fibrotic features and TGF-β signalling in metastatic livers of CRC. Results: POSTN deficiency reduced hepatic stellate cell (HSC) activation and liver metastasis, whereas POSTN overexpression in the liver significantly augmented the formation of a fibrotic microenvironment to support the liver metastatic growth of CRC cells in mice. Moreover, HSC-derived POSTN promoted TGF-β1 expression in CRC cells through the integrin/FAK/ERK/STAT3 pathway; conversely, tumour cell-derived TGF-β1 induced POSTN expression in HSCs via the Smad pathway. POSTN levels correlated with fibrotic features and TGF-β signalling in metastatic liver tissues of CRC patients. Conclusions: POSTN and TGF-β1 cooperatively contribute to the tumour-stroma crosstalk by forming a supporting fibrotic microenvironment to promote liver metastasis of CRC cells via the POSTN/integrin/FAK/ERK/STAT3/TGF-β axis in tumour cells and TGF-β/Smad/POSTN signalling in activated HSCs. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00070920
- Volume :
- 130
- Issue :
- 3
- Database :
- Academic Search Index
- Journal :
- British Journal of Cancer
- Publication Type :
- Academic Journal
- Accession number :
- 175753011
- Full Text :
- https://doi.org/10.1038/s41416-023-02516-3