Commensal dysbiosis promotes the development of colorectal cancer liver Metastasis via the C–C chemokine ligand 6/C–C chemokine receptor 1 axis
Year: 2025
Type: article
Abstract: BACKGROUND: Gut microorganisms are involved in the occurrence and progression of various types of cancer, including colorectal cancer. Previous studies have shown that the disruption of commensal homeostasis can promote tumor metastasis. The present study aimed to investigate the effects of gut commensal dysbiosis on the risk of colorectal cancer liver metastasis (CRLM) and its mechanisms. MATERIALS AND METHODS: A mouse model of CRLM with the commensal dysbiosis background was established. This model was used to investigate the impact of commensal dysbiosis on CRLM. RESULTS: Commensal dysbiosis promoted CRLM development via the C-C chemokine ligand 6 ( CCL6 ) and C-C chemokine receptor 1 ( CCR1 ) axis. Moreover, it altered the liver tumor microenvironment (TME) by recruiting tumor-associated macrophages (TAMs), notably M2-like TAMs, and promoted liver metastasis growth. Liver metastasis was promoted via the upregulation of CCL6 expression levels, which resulted in CCR1 +TAM infiltration into the TME. Notably, inhibiting CCR1 expression could reduce CRLM. CONCLUSION: Commensal dysbiosis could promote CRLM development via CCL6/CCR1 signaling. Targeting this signaling axis could be an effective method to inhibit CRLM by regulating the TME.
Language: English
Topic: Gut microbiota and health
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: diamond
OpenAlex ID: W4415523360