Kinesin family member 23 exerts a protumor function in breast cancer via stimulation of the Wnt/β-catenin pathway

被引：6
作者：
He, Xin [1 ]
Wang, Juan [1 ]
Zhou, Ru [1 ]
Yu, Shanshan [1 ]
Jiang, Jue [1 ]
Zhou, Qi [1 ]
机构：
[1] Xi An Jiao Tong Univ, Dept Ultrasound, Affiliated Hosp 2, 157 Xiwu Rd, Xian 710004, Shaanxi, Peoples R China
来源：
TOXICOLOGY AND APPLIED PHARMACOLOGY | 2022年 / 435卷
关键词：
Breast cancer; KIF23; Wnt; PROMOTE CELL-PROLIFERATION; KIF23; OVEREXPRESSION; EXPRESSION; PROGNOSIS;
D O I：
10.1016/j.taap.2021.115834
中图分类号：
R9 [药学];
学科分类号：
1007 ;
摘要：
Kinesin family member 23 (KIF23) has been described as one of the main genes that are associated with ma-lignant transformation in numerous cancers. However, the exact significance of KIF23 in breast cancer has not been well-addressed. The present study was dedicated to the comprehensive investigation of KIF23 in breast cancer. Initial expression analysis through The Cancer Genome Atlas (TCGA) demonstrated high KIF23 levels in breast cancer compared with normal controls. These in silico data showing high levels of KIF23 in breast cancer were verified by assessing clinical specimens using real-time quantitative PCR and immunoblot assays. Moreover, a high KIF23 level was correlated with adverse clinical outcomes in breast cancer patients. Cellular functional experiments showed that the down-regulation of KIF23 affected the malignant behaviors of breast cancer cells in vitro, whereas the forced expression of KIF23 stimulated them. Mechanistic studies revealed that KIF23 restraint down-regulated the levels of phosphorylated glycogen synthetase kinase-3 beta (GSK-3 beta), beta-catenin, cyclin D1 and c-myc in breast cancer cells, showing an inhibitory effect on the Wnt/beta-catenin pathway. The suppression of GSK-3 beta was able to reverse KIF23-silencing-induced inactivation of the Wnt/beta-catenin pathway. Inhibition of the Wnt/beta-catenin pathway abolished KIF23 overexpression-mediated protumor effects in breast cancer. A xenograft assay confirmed the in vivo antitumor function of KIF23 inhibition. In conclusion, these findings suggest that KIF23 may exert a protumor function in breast cancer by stimulating the Wnt/beta-catenin pathway. This work suggests that KIF23 has potential values for targeted therapy and prognosis in breast cancer.
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页数：13
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