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

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.

Jiang J ，Wang J ，He X ，Ma W ，Sun L ，Zhou Q ，Li M ，Yu S ... -  《-》

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

MicroRNA-367-3p (miR-367-3p) has been previously reported as a cancer-related miRNA that is dysregulated in various cancer types and functions either as an oncogenic or as tumour suppressive miRNA. However, whether miR-367-3p is dysregulated in cervical cancer and, further, whether it contributes to the development and progression of the disease remains unknown. Here, our results demonstrated that miR-367-3p expression was markedly decreased in both cervical cancer tissues and cell lines compared with corresponding controls. In vitro experiments revealed that miR-367-3p overexpression repressed the proliferation and invasion of cervical cancer cells. Notably, sperm-associated antigen 5 (SPAG5) was identified as a target gene of miR-367-3p. Moreover, decreased expression of miR-367-3p was correlated with high expression of SPAG5 in cervical cancer tissue specimens. SPAG5 inhibition or miR-367-3p overexpression significantly downregulated Wnt/β-catenin signalling in cervical cancer cells. However, the antitumour effect mediated by miR-367-3p overexpression was partially reversed by SPAG5 overexpression. Overall, these findings demonstrate that miR-367-3p overexpression restricts the proliferation and invasion of cervical cancer cells through targeting SPAG5 to downregulate Wnt/β-catenin signalling, suggesting a mechanism for the tumour suppressive function of miR-367-3p in cervical cancer. Our study highlights the involvement of miR-367-3p/SPAG5/Wnt/β-catenin signalling axis in regulating the malignant progression of cervical cancer.

Yang T ，Tian S ，Wang L ，Wang Y ，Zhao J ... -  《-》

SPAG5 contributes to the progression of gastric cancer by upregulation of Survivin depend on activating the wnt/β-catenin pathway.

The sperm-associated antigen 5 (SPAG5) plays a key role in controlling cellular processes, including cell cycle progression and proliferation. However, the role of SPAG5 in gastric cancer (GC) remains unclear. Herein, our study showed that upregulation of SPAG5 was detected frequently in GC tissues, and was associated with significantly worse survival in patients with GC. Multivariate analyses revealed that high SPAG5 expression was an independent predictive marker for the poor prognosis of GC patients. Further, SPAG5 knockdown notably inhibited the proliferation abilities of GC in vivo and in vitro. Moreover, our results indicate that SPAG5 promotes cell progression by increasing Survivin expression, which has been reported to control the progression of GC. Moreover, our data demonstrate that Survivin is crucial for SPAG5-mediated GC cell progression in vitro and in vivo. Mechanistically, we demonstrated that SPAG5 promotes the progression of GC via enhancing the Wnt/β-catenin/Survivin axis. Collectively, our data suggest that SPAG5 plays a crucial oncogenic role in GC tumorigenesis, and we provide a novel evidence that SPAG5 may be serve as a prognostic and therapeutic target for GC patients.

Liu G ，Liu S ，Cao G ，Luo W ，Li P ，Wang S ，Chen Y ... -  《-》

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)-3β phosphorylation and downregulate active β-catenin protein expression, thereby leading to repression of β-catenin transcriptional activity. Activation of Wnt/β-catenin signalling by treatment of GSK-3β 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/β-catenin signalling, suggesting ST7L as a potential therapeutic target for breast cancer.

Wang H ，Sun L ，Jiang J ，Yu S ，Zhou Q ... -  《-》

SPAG5 promotes hepatocellular carcinoma progression by downregulating SCARA5 through modifying β-catenin degradation.

Liu H ，Hu J ，Wei R ，Zhou L ，Pan H ，Zhu H ，Huang M ，Luo J ，Xu W ... -  《JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH》