Long chain fatty acid transport via SLC27A1 enhances DAG-3-P synthesis and accelerates colorectal cancer metastasis

Colorectal cancer (CRC) is a major global health issue. Despite advancements in treatment, CRC patients still face challenges of metastasis and variable prognosis. Circulating tumor cells (CTCs) shed from the primary tumor into the peripheral blood circulation provide new insights into the potential molecular mechanisms driving tumor progression and metastasis.In this study, we comprehensively analyzed CTC data, primary tumor tissue data, and metastatic tumor tissue data from CRC patients to identify pathways associated with CRC metastasis, with a specific focus on the transport processes of vitamins, nucleosides, and related molecules. Using machine learning techniques, we identified Solute Carrier Family 27 Member 1 (SLC27A1) as the biomarker most closely associated with CRC metastasis. SLC27A1 is responsible for transporting extracellular long-chain fatty acids (LCFAs) into cells, and the model constructed based on the expression level of this gene achieved an accuracy of over 95% in assisting the assessment of patients' metastatic risk across different datasets.Further studies revealed that the process of intracellular LCFAs being catalyzed to synthesize diacylglycerol-3-phosphate (DAG-3P) is closely related to CRC metastasis. Laboratory experiments confirmed that downregulation of SLC27A1 expression in colorectal cancer cell lines (Caco-2 and T84) significantly inhibited cell migration and invasion abilities, directly validating the functional role of this gene in promoting tumor metastasis. Additionally, statistical analysis using data from the National Health and Nutrition Examination Survey database (2017-2020) showed a slightly higher incidence of cancer in populations with high-fat intake.These findings, integrating computational predictions and experimental validation, deepen our understanding of the biological mechanisms of colorectal cancer and provide potential targets for therapeutic interventions and personalized treatment strategies.