1. Department of Breast and Thyroid Surgery, Zhongnan Hospital, Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study Center, Wuhan University, Wuhan 430071, Hubei, China;
2. Department of Pathology and Pathophysiology, Hubei Provincial Key Laboratory of Developmentally Originated Disease, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, Hubei, China;
3. Department of Anatomy, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, Hubei, China.
Background: Breast cancer is the highest incidence of tumor in women, which seriously threaten women's health. The occurrence and progression of breast cancer is linked to inactivation or downregulation of tumor suppressors, and activation or upregulation of oncogenes. However, the mechanism of PAK7 involving in the occurrence and progression of breast cancer is not yet fully understood.
Methods: PAK7 expression was analyzed by RT-qPCR and immunohistochemistry and correlated with clinicopatholgical parameters in breast cancer tissue microarray. The effects of PAK7 on breast cancer cells were detected by CCK-8 assay, colon formation assay, wound healing and transwell assays, and flow cytometry. The relationship between PAK7 and Wnt/β-catenin signaling pathway was determined by western blotting, TOP/FOP flash, co-Immunoprecipitation and co-localization assays.
Results: PAK7 expression was significantly increased in breast cancer tissues and positively correlated with pathological differentiation and TNM stage of breast cancer. Overexpression of PAK7 could significantly promote proliferation and migration of breast cancer cells, and inhibit apoptosis. In contrast, PAK7 knockdown significantly inhibited the proliferation and migration of breast cancer cells and promoted apoptosis. In addition, PAK7 could activate Wnt/β-catenin signaling pathway in breast cancer cells. Further study found that PAK7 could directly bind to GSK3β and β-catenin, and regulate β-catenin degradation by phosphorylating GSK3β.
Conclusions: Our study demonstrated that PAK7, as an oncogene, involved in breast cancer progression by activating the Wnt/β-catenin signaling pathway, suggesting that the potential applicability of PAK7 as a target for breast cancer treatment.
Keywords: P21-activated kinase 7, Wnt/β-catenin signaling pathway, cell proliferation, cell migration, breast cancer