Periostin-TGF-β feedforward loop contributes to tumour-stroma crosstalk in liver metastatic outgrowth of colorectal cancer
© 2023. The Author(s), under exclusive licence to Springer Nature Limited..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:130 |
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| Enthalten in: |
British journal of cancer - 130(2024), 3 vom: 14. Feb., Seite 358-368 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Liu, Bin [VerfasserIn] |
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| Links: |
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| Themen: |
Integrins |
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| Anmerkungen: |
Date Completed 13.02.2024 Date Revised 05.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s41416-023-02516-3 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a Periostin-TGF-β feedforward loop contributes to tumour-stroma crosstalk in liver metastatic outgrowth of colorectal cancer |
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| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023. The Author(s), under exclusive licence to Springer Nature Limited. | ||
| 520 | |a 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) | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
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| 650 | 7 | |a Periostin |2 NLM | |
| 650 | 7 | |a Transforming Growth Factor beta |2 NLM | |
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| 700 | 1 | |a Lin, Biyu |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Xingxing |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Yingfu |e verfasserin |4 aut | |
| 700 | 1 | |a Song, Gang |e verfasserin |4 aut | |
| 700 | 1 | |a Fan, Chuannan |e verfasserin |4 aut | |
| 700 | 1 | |a Ouyang, Gaoliang |e verfasserin |4 aut | |
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