Targeting TPX2 suppresses proliferation and promotes apoptosis via repression of the PI3k/AKT/P21 signaling pathway and activation of p53 pathway in breast cancer

被引:45
作者
Chen, Miaomiao [1 ,2 ]
Zhang, Hongqin [1 ,2 ]
Zhang, Guihong [1 ,2 ]
Zhong, Ailing [1 ,2 ]
Ma, Qian [1 ,2 ]
Kai, Jinyan [1 ,2 ]
Tong, Yin [1 ]
Xie, Suhong [1 ]
Wang, Yanchun [1 ]
Zheng, Hui [1 ]
Guo, Lin [1 ,2 ]
Lu, Renquan [1 ,2 ]
机构
[1] Fudan Univ, Dept Clin Lab, Shanghai Canc Ctr, 270,Dong An Rd, Shanghai 200032, Peoples R China
[2] Fudan Univ, Shanghai Med Coll, Dept Oncol, Shanghai, Peoples R China
基金
中国国家自然科学基金;
关键词
TPX2; Breast cancer; Cell apoptosis; AKT signaling pathway; p53; PROTEIN; GROWTH; CONTRIBUTES;
D O I
10.1016/j.bbrc.2018.10.164
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Targeting protein for Xenopus kinesin-like protein 2 (TPX2) is a microtubule-associated protein required for mitosis and spindle assembly. Previous studies showed that TPX2 is overexpressed in various human cancers and promotes cancer progression. In this study, the differentially expressed genes including TPX2 were screened in GEO database for gene expression microarray of breast cancer. The TPX2 expression level was significantly increased in breast cancer cells and the breast malignant tissues compared with those controls. In vitro experiment further confirmed that knockdown of TPX2 by small hairpin RNA inhibited breast cancer cell proliferatio, migration, and induced cell apoptosis. TPX2 silencing decreased the expression of PI3K and extent of AKT phosphorylation, as well as increased expression of p53 and p21. Taken together, our findings indicate that TPX2 silencing negatively regulates the PI3K/AKT and activates p53 signaling pathway by which breast cancer cells proliferation were inhibited whereas cellulars apoptosis were accelerated, suggesting that TPX2 may be a potential target for anticancer therapy in breast cancer. (C) 2018 Published by Elsevier Inc.
引用
收藏
页码:74 / 82
页数:9
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