PDK4-driven metabolic reprogramming enhances mesothelial cell invasion in colorectal cancer peritoneal metastasis

• PDK4 is identified as a key gene in mesothelial cells during colorectal cancer peritoneal metastasis, with elevated expression in cells undergoing mesothelial-to-mesenchymal transition (MMT). • PDK4 promotes mesothelial cell invasion by enhancing fatty acid oxidation (FAO), which is essential for the invasive phenotype. • PDK4-driven FAO leads to increased acetylation of β-catenin, a modification critical for mesothelial cell invasion. • Targeting PDK4 or FAO may offer a novel therapeutic strategy to inhibit peritoneal metastasis in colorectal cancer.