LYAR promotes colorectal cancer progression by up-regulating FSCN1 expression and is closely related to fatty acid metabolism

Colorectal cancer (CRC) is a highly malignant tumor associated with a poor prognosis, yet the molecular mechanisms are not fully understood. In this study, we showed that LYAR expresses at a higher level in CRC than normal tissue and LYAR expression is closely associated with distant CRC metastasis. LYAR significantly promotes the migration and invasion of CRC cells in vitro, and reduction of LYAR expression in CRC cells inhibites xenograft tumor metastasis in vivo. Microarray analysis of LYAR knockdown (KD) cells combined with ChIP assay, gene reporter assay and rescue experiment indicate that FSCN1 (fascin actin-bundling protein 1, Fascin-1) serves as a new and key regulator of the LYAR-promoted migration and invasion of CRC cells. In addition, knockdown of FSCN1 significantly inhibites subcutaneous tumorigenesis of CRC cells. Moreover, we found that FSCN1 affects some key enzymes in lipid fatty acid metabolism such as FASN and SCD. In summary, this study reveals a novel mechanism by which LYAR promotes tumor cell migration and invasion by up-regulating FSCN1 expression and further promoting fatty acid synthesis in CRC. Overall design: RNA-sequencing of NC cells and FSCN1 siRNA cells