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Abstract
The mitochondrial enzyme ALDH6A1 is identified as an anti-invasive factor in gastric cancer metastasis.
- ALDH6A1 down-regulation leads to the accumulation of methylmalonic acid (MMA).
- MMA inhibits the histone demethylase KDM5C, resulting in increased levels of H3K4 dimethylation (H3K4me2) at invasion-related gene promoters.
- Genes affected by this mechanism include ANGPT2 and MMP7, which are associated with cancer invasion.
- In mice, this epigenetic reprogramming promotes liver metastasis of gastric cancer.
- Activation of ALDH6A1 or clearance of MMA reduces H3K4me2 levels and metastatic burden.
Simplified
CRISPR Gene Editing