SREBP1 silencing inhibits the proliferation and motility of human esophageal squamous carcinoma cells via the Wnt/β-catenin signaling pathway

Sterol regulatory element-binding protein 1 (SREBP1) is dysregulated in a variety of types of human cancer. However, the functional roles of SREBP1 in esophageal squamous cell carcinoma (ESCC) remain poorly understood. The present study investigated the function of SREBP1 in cell proliferation and motility. Microarray datasets in Oncomine, reverse transcription-quantitative PCR and western blot analysis revealed that SREBP1 was overexpressed in ESCC tumors when compared with normal tissues. In addition, SREBP1 overexpression was significantly associated with tumor differentiation, lymphatic metastasis and Ki67 expression. Results suggested that silencing SREBP1 inhibited the proliferation, migration and invasion of ESCC cells, whereas overexpression of SREBP1 had opposite effects on proliferation and metastasis. In addition, loss of SREBP1 significantly increased E-cadherin and decreased N-cadherin, Vimentin, Snail, matrix metalloproteinase 9 and vascular endothelial growth factor C expression levels, which were restored via SREBP1-overexpression. Mechanistically, loss of SREBP1 suppressed T-cell factor 1/lymphoid enhancer factor 1 (TCF1/LEF1) activity and downregulated TCF1/LEF1 target proteins, including CD44 and cyclin D1. Moreover, knockdown of SREBP1 downregulated the expression levels of stearoyl-CoA desaturase 1 (SCD1), phosphorylated glycogen synthase kinase-3β and nuclear β-catenin. Furthermore, the inhibitors of SREBP1 and/or SCD1 and small interfering RNA-SCD1 efficiently inhibited the activation of the Wnt/β-catenin pathway driven by constitutively active SREBP1. Finally, in vivo results indicated that SREBP1-knockdown suppressed the proliferation and metastasis of ESCC. Taken together, these findings demonstrated that SREBP1 exerts oncogenic effects in ESCC by promoting proliferation and inducing epithelial-mesenchymal transition via the SCD1-induced activation of the Wnt/β-catenin signaling pathway.