LYAR Promotes Colorectal Cancer Progression by Upregulating <i>FSCN1</i> Expression and Fatty Acid Metabolism

Abstract

Colorectal cancer (CRC) is a highly malignant tumor associated with poor prognosis, yet the molecular mechanisms are not fully understood. In this study, we showed that LYAR, a nucleolar protein, is expressed at a higher level in CRC tissue than in adjacent normal tissue and that LYAR expression is closely associated with distant CRC metastasis. LYAR not only significantly promotes the migration and invasion of CRC cells <i>in vitro</i>, but knockdown (KD) of LYAR in CRC cells also inhibits xenograft tumor metastasis <i>in vivo</i>. Microarray analysis of <i>LYAR</i> KD cells combined with a chromatin immunoprecipitation (ChIP) assay, gene reporter assay, and rescue experiment indicated that <i>FSCN1</i> (encoding fascin actin-bundling protein 1 (Fascin-1)) serves as a novel key regulator of LYAR-promoted migration and invasion of CRC cells. Knockdown of <i>FSCN1</i> significantly inhibits subcutaneous tumorigenesis of CRC cells and leads to the downregulation of <i>FASN</i> and <i>SCD</i>, genes encoding key enzymes in fatty acid synthesis. In summary, this study reveals a novel mechanism by which LYAR promotes tumor cell migration and invasion by upregulating <i>FSCN1</i> expression and affecting fatty acid metabolism in CRC.