L1CAM drives oncogenicity in esophageal squamous cell carcinoma by stimulation of ezrin transcription

L1 cell adhesion molecule (l1cam) is highly expressed in various types of human cancers, displaying yet unknown molecular mechanisms underlying their oncogenic potential. here, we found that l1cam expression was significantly increased in esophageal squamous cell carcinoma (escc; n = 157) lesions compared with non-cancerous tissues. high tumorous l1cam expression significantly correlated with reduced overall survival. experimentally, l1cam knockdown led to decreased cell growth, migration, and invasiveness in vitro, whereas overexpression of l1cam showed the opposite effect. in nude mice, l1cam depletion attenuated tumorigenesis and ability to penetrate the tissues surrounding escc cells. gene set enrichment analysis (gsea) and subpathwayminer analysis on gene expression profiles (microarray data on escc tissues, gse53625; cdna microarray data on l1cam-knockdown escc cell line, gse86268) suggested that l1cam-co-expression genes were related to cell motility, cell proliferation, and regulation of actin cytoskeleton, validating the above experimental findings. further mechanistical analysis showed that l1cam upregulated the expression of the cytoskeletal protein ezrin via activating integrin β1/mapk/erk/ap1 signaling and thus led to the malignant phenotypes of escc cells. together, our findings suggest that l1cam be employed as a valuable prognosis marker and a therapeutic target for escc patients and that l1cam promotes escc tumorigenicity by upregulating ezrin expression.