KLK11 suppresses cellular proliferation via inhibition of Wnt/β-catenin signaling pathway in esophageal squamous cell carcinoma.

Studies have demonstrated that kallikrein-associated peptidase 11 (KLK11) is dysregulated in various cancers. However, the potential roles of KLK11 in esophageal squamous cell carcinoma (ESCC) are still unknown. In our study, we found that the expression of KLK11 in advanced ESCC was significantly down regulated than that in the adjacent tissues, and patients with higher KLK11 expression had markedly increased overall survival rates compared with those with lower KLK11 expression. In addition, up regulation of KLK11 decreased the proliferation capacity of TE-1 and EC18 cells, and down regulation of KLK11 increased the proliferation capacity. To explore the possible mechanism of KLK11 in regulating the proliferation of ESCC, the expression of the related factors in Wnt/β-catenin pathway and cell cycle-mediated factors, such as GSK-3β/p-GSK-3β, β-catenin, Ki67, p-Rb/Rb, CDK6, CDK4 and Cyclin D1, were determined. Furthermore, KLK11 was found to be negatively correlated with the expression of β-catenin in the nucleus, as showed by decreased expression of cyclin D1 and Ki67 through deactivation of the Wnt/β-catenin signaling pathway. XAV-939, a Wnt/β-catenin inhibitor, partially decreased the effects of KLK11 deficiency on ESCC cell proliferation. Finally, we validated that KLK11 inhibited ESCC proliferation in vivo. Our results showed that the inhibitory effects of KLK11 on the proliferation of TE-1 and EC18 cells might be associated with inhibition of Wnt/β-catenin signaling pathway. KLK11 played a key role in inhibiting ESCC carcinogenesis and progression and became a potential biomarker for poor prognosis in patients with ESCC. AJCR