Suppression of the proliferation and invasion of breast cancer cells by ST7L occurs through inhibition of activation of Wnt/GSK-3β/β-catenin signalling

Emerging evidence has indicated that suppression of tumorigenicity 7-like (ST7L) is a tumour suppressor in multiple types of cancers. However, the functional involvement of ST7L has not been studied in breast cancer. In the present study, we aimed to investigate the potential biological function of ST7L in breast cancer. Herein, we found that ST7L expression was frequently downregulated in breast cancer cell lines. Functional assays revealed that ST7L overexpression significantly inhibited the proliferation and invasion of breast cancer cells, while ST7L silencing showed opposite effect. Notably, ST7L was found to decrease glycogen synthase kinase (GSK)-3 beta phosphorylation and downregulate active beta-catenin protein expression, thereby leading to repression of beta-catenin transcriptional activity. Activation of Wnt/beta-catenin signalling by treatment of GSK-3 beta inhibitor significantly abrogated ST7L-mediated antitumour effect. Additionally, ST7L overexpression blunted the tumorigenicity of breast cancer cells in vivo in xenograft mice. Taken together, our results demonstrate that ST7L exerts antitumor function in breast cancer associated with the suppression of Wnt/beta-catenin signalling, suggesting ST7L as a potential therapeutic target for breast cancer.