Ketogenic diet impairs NK cell cytotoxic function in colorectal cancer liver metastasis by inducing ferroptosis via suppression of the p62-Keap1-Nrf2 pathway.

ABSTRACT: Emerging evidence suggests the ketogenic diet (KD) may modulate cancer progression, though its impact on colorectal cancer liver metastasis (CRLM) remains poorly characterized. Our study demonstrates that a KD promotes CRLM in a mouse model. Untargeted metabolomics identifies specific phosphatidylethanolamine (PE) metabolites as key mediators of this effect. Using single-cell RNA sequencing (scRNA-seq) and flow cytometry, we find that enhanced metastasis critically depends on KD-induced impairment of NK cell cytotoxicity and viability. This aligns with reduced NK cell numbers within the tumor microenvironment (TME) of CRLM patients compared to non-metastatic CRC patients, as shown by immunofluorescence staining. Further analysis reveals that PE compromises NK cell anti-tumor function both

SUBMITTER: Cai R 

PROVIDER: S-EPMC12757549 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature