High expression of SPAG SPAG 5 sustains the malignant growth and invasion of breast cancer cells through the activation of Wnt/β‐catenin signalling

摘要

Summary Sperm‐associated antigen 5 ( SPAG 5) has currently emerged as a novel oncogene in various cancers. High expression of SPAG 5 has been frequently detected in breast cancer. However, the biological function and regulatory mechanism of SPAG 5 in breast cancer remain unclear. In this study, we aimed to investigate the potential biological function of SPAG 5 in breast cancer cells. Herein, we found that both the mRNA and protein expression of SPAG 5 were significantly up‐regulated in breast cancer cell lines. Functional experiments showed that silencing of SPAG 5 inhibited the proliferation and invasion of breast cancer cells, while the overexpression of SPAG 5 promoted the proliferation and invasion of breast cancer cells. Mechanistic investigation demonstrated that SPAG 5 promoted the expression of Wnt3 and β‐catenin, and increased the activation of β‐catenin/ TCF 4 transcriptional activity. Notably, the inhibition of Wnt3 partially reversed the promotion effect of SPAG 5 on breast cancer cell proliferation and invasion and β‐catenin/ TCF 4 signalling. In addition, the inhibition of β‐catenin also significantly abrogated SPAG 5‐mediated oncogenic effects in breast cancer. Taken together, these findings demonstrate that SPAG 5 promotes the proliferation and invasion of breast cancer cells by activating Wnt/β‐catenin signalling via up‐regulating Wnt3 expression.