Clinical significance of L1CAM expression and its biological role in the progression of oral squamous cell carcinoma

Abstract

L1 cell adhesion molecule (L1CAM) has been implicated in the progression and metastasis of numerous cancers. However, the role of L1CAM in oral squamous cell carcinoma (OSCC) is not well characterized. In the present study, the expression of L1CAM was examined in oral tongue squamous cell carcinoma (OTSCC) tissue samples by immu- nohistochemistry, the clinicopathological significance of L1CAM expression was evaluated by chi-squared test, and the overall survival (OS) rate was analyzed using Kaplan-Meier method according to the expression of L1CAM. In addition, it was aimed to elucidate the biological role of L1CAM and the underlying molecular mechanisms by which L1CAM functions in OSCC cells in relation to epithelial-mesenchymal transition (EMT) and PI3K/AKT/ERK signaling pathways. Thus, the functions of L1CAM on the OSCC cell prolifera- tion, migration and invasion, and the activation of EMT and PI3K/AKT/ERK signaling pathways were investigated in vitro. Positive L1CAM expression was found in 32.5% of OTSCC cases and was significantly correlated with high histologic grade, greater depth of invasion, lymph node metastasis, peri- neural invasion, advanced stage, and survival status. Patients with positive L1CAM expression had significantly lower OS rate. Particularly in patients with early OTSCC, L1CAM expression was strongly associated with worse prognosis. Overexpression of the recombinant human L1CAM protein significantly increased cell proliferation, migration and inva- sion. By contrast, L1CAM knockdown using small interfering RNA significantly inhibited cell proliferation, migration, inva- sion and EMT. Moreover, phosphorylated (p)-PI3K, p-AKT and p-ERK expression levels were significantly reduced by L1CAM knockdown. Taken together, the findings of the present study suggested that L1CAM could be a potential prognostic marker and a promising therapeutic target in OSCC.