STEAP1 Suppresses Oral Squamous Cell Carcinoma by Targeting Wnt/β‐Catenin Signalling and EMT

OBJECTIVE: The present study aimed to investigate the expression and biological behaviour of the six-transmembrane epithelial antigen of the prostate 1 (STEAP1) in oral squamous cell carcinoma (OSCC), and to further analyse its underlying mechanisms. MATERIAL AND METHODS: Western blot and immunohistochemistry were used to detect protein expression. After overexpression of STEAP1 in OSCC cells by plasmid transfection, cell proliferation, migration, and invasion abilities were assessed using CCK-8, scratch, and Transwell assays, respectively, and ROS levels were detected using the corresponding kits. Finally, the expression changes of EMT and Wnt/β-catenin pathway-related proteins were analysed by Western blot. RESULT: Western blot (WB) and immunohistochemical (IHC) analyses showed that STEAP1 was significantly underexpressed (p < 0.0001) in oral squamous cell carcinoma (OSCC) tissues and cell lines (SAS, Tca-8113, SCC15) compared to normal controls. Functional experiments showed that overexpression of STEAP1 effectively inhibited the proliferation (p < 0.001), migration (p < 0.0001), and invasion (p < 0.001) abilities of OSCC cells (SAS, Tca-8113) and reduced intracellular ROS levels (p < 0.0001). Molecularly, STEAP1 overexpression up-regulated E-cadherin (p < 0.01) and down-regulated N-cadherin (p < 0.05), inhibiting the EMT process; meanwhile, it decreased the protein levels of β-catenin (p < 0.05), Axin2 (p < 0.05), and c-Myc (p < 0.05), as well as the protein levels of the p- GSK3β/T-GSK3β ratio (p < 0.05), but there was no significant change in total GSK3β protein, suggesting inhibition of the Wnt/β-catenin pathway. CONCLUSION: STEAP1 is downregulated in OSCC and suppresses malignant phenotypes of OSCC cells in vitro, with effects associated with EMT-related changes and attenuation of Wnt/β-catenin-associated signalling.