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Inhibition of PCSK9 Attenuates Liver Endothelial Cell Activation Induced by Colorectal Cancer Stem Cells during Liver Metastasis

ABSTRACT: Colorectal cancer often leads to liver metastases, a major cause of patient mortality. This study investigates the role of PCSK9, a protein traditionally known for its role in cholesterol metabolism, in the metastatic process. Researchers found that conditioned media from colorectal cancer stem cell strongly upregulates PCSK9 expression in liver sinusoidal endothelial cells (LSECs). PCSK9 activation enhances LSEC proliferation and migration, contributing to the formation of a pro-metastatic niche. Inhibiting PCSK9 with the small molecule PF-06446846 reduced endothelial activation and normalized gene expression, decreasing LSEC potential support of the metastatisis. Immunofluorescence confirmed PCSK9 expression in Liver Endothelial Cells (LSEC)s of human colorectal cancer liver metastases. These results suggest that PCSK9 could represent a promising therapeutic target to prevent and treat liver metastases in colorectal cancer patients.

ORGANISM(S): Homo sapiens

PROVIDER: GSE299058 | GEO | 2025/07/02

REPOSITORIES: GEO

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