High expression of SPAG5 sustains the malignant growth and invasion of breast cancer cells through the activation of Wnt/β‐catenin signalling

Abstract

Summary Sperm‐associated antigen 5 (SPAG5) has currently emerged as a novel oncogene in various cancers. High expression of SPAG5 has been frequently detected in breast cancer. However, the biological function and regulatory mechanism of SPAG5 in breast cancer remain unclear. In this study, we aimed to investigate the potential biological function of SPAG5 in breast cancer cells. Herein, we found that both the mRNA and protein expression of SPAG5 were significantly up‐regulated in breast cancer cell lines. Functional experiments showed that silencing of SPAG5 inhibited the proliferation and invasion of breast cancer cells, while the overexpression of SPAG5 promoted the proliferation and invasion of breast cancer cells. Mechanistic investigation demonstrated that SPAG5 promoted the expression of Wnt3 and β‐catenin, and increased the activation of β‐catenin/TCF4 transcriptional activity. Notably, the inhibition of Wnt3 partially reversed the promotion effect of SPAG5 on breast cancer cell proliferation and invasion and β‐catenin/TCF4 signalling. In addition, the inhibition of β‐catenin also significantly abrogated SPAG5‐mediated oncogenic effects in breast cancer. Taken together, these findings demonstrate that SPAG5 promotes the proliferation and invasion of breast cancer cells by activating Wnt/β‐catenin signalling via up‐regulating Wnt3 expression.

MicroRNA‐367‐3p overexpression represses the proliferation and invasion of cervical cancer cells through downregulation of SPAG5‐mediated Wnt/β‐catenin signalling

“…Importantly, multiple studies have revealed that the oncogenic function of SPAG5 is associated with the activation of Wnt/β‐catenin signalling. It is reported that SPAG5 can upregulate the expression of Wnt3 and contribute to the activation of Wnt/β‐catenin signalling in both bladder and breast cancer cells . In hepatocellular carcinoma cells, SPAG5 promotes the accumulation of β‐catenin through decreasing the expression of scavenger receptor class A member 5 .…”

“…Sperm‐associated antigen 5 (SPAG5) has been recently identified as a novel regulator of tumorigenesis . SPAG5 was originally identified as a mitotic spindle‐associated protein that regulates the timing of spindle organization and sister chromatid cohesion .…”

Astrin: A Key Player in Mitosis and Cancer

“…Astrin, which is an essential mitotic protein has been found to display abnormally high expression and is associated with tumor prognoses in many cancers ( Abdel-Fatah et al, 2016 ; Liu H. et al, 2018 ; Liu J. Y. et al, 2018 ; Liu et al, 2019 ; Zhang et al, 2020 ). Current research has found that Astrin plays a key role in activating many signaling pathways that are known to be associated with cancer, including the WNT/β-catenin and PI3K/AKT signaling pathways ( Yang et al, 2018 ; Jiang et al, 2019 ). This informs us that the important mitotic protein Astrin may instigate an unusual role in cancer development.…”

“…Specifically, copy number mutations of Astrin and its high transcriptional and protein expression were linked to a shorter survival period and a poorer prognosis in breast cancer patients. High expression of Astrin was associated with both malignancy and invasiveness of breast cancer, and often led to a higher risk of recurrence and lymphatic metastasis ( Jiang et al, 2019 ; Li et al, 2019 ).…”

“…Overexpressed Astrin also increased the expression of Wnt family member 3 (WNT3) and β-catenin, activating the WNT/β-catenin signaling pathway ( Jiang et al, 2019 ). In addition, Astrin was found to interact with MYCBP to promote the transcriptional activity of c-MYC , which could promote cell proliferation via upregulating c-MYC targeted genes including CDC20 , CDC25C , breast-cancer susceptibility gene (BRCA) 1, and BRCA2 in triple-negative breast cancer ( Li et al, 2019 ).…”