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:42
|
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
相关论文
共 50 条
  • [1] Resveratrol mediated the proliferation and apoptosis of gastric cancer cells by modulating the PI3K/Akt/P53 signaling pathway
    Dong, Qihao
    Zheng, Aixi
    Zhai, Heng
    Zhang, Tongtong
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2024, 723
  • [2] TPX2 promotes glioma cell proliferation and invasion via activation of the AKT signaling pathway
    Gu, Jian-Jun
    Zhang, Jian-He
    Chen, Hong-Jie
    Wang, Shou-Sen
    ONCOLOGY LETTERS, 2016, 12 (06) : 5015 - 5022
  • [3] Apatinib suppresses the proliferation and apoptosis of gastric cancer cells via the PI3K/Akt signaling pathway
    Jia, Xiaoqiong
    Wen, Zhenping
    Sun, Qiuying
    Zhao, Xiaohua
    Yang, Hao
    Shi, Xiaoyu
    Xin, Tao
    JOURNAL OF BUON, 2019, 24 (05): : 1985 - 1991
  • [4] TIM-1 promotes proliferation and metastasis, and inhibits apoptosis, in cervical cancer through the PI3K/AKT/p53 pathway
    Liuyan Chen
    Jilin Qing
    Yangyang Xiao
    Xiaomei Huang
    Yanlin Chi
    Zhizhong Chen
    BMC Cancer, 22
  • [5] TIM-1 promotes proliferation and metastasis, and inhibits apoptosis, in cervical cancer through the PI3K/AKT/p53 pathway
    Chen, Liuyan
    Qing, Jilin
    Xiao, Yangyang
    Huang, Xiaomei
    Chi, Yanlin
    Chen, Zhizhong
    BMC CANCER, 2022, 22 (01)
  • [6] In vitro anticancer study of novel curcumin derivatives via targeting PI3K/Akt/p53 signaling pathway
    Zhou, Huixian
    Wu, Zhiwen
    Zhang, Yannan
    Yu, Zikai
    Nie, Zhengyang
    Fan, Jinbiao
    Zhu, Zuchang
    Chen, Fenglian
    Wang, Tao
    MOLECULAR DIVERSITY, 2025, 29 (01) : 73 - 86
  • [7] Paclitaxel inhibits proliferation and invasion and promotes apoptosis of breast cancer cells by blocking activation of the PI3K/AKT signaling pathway
    Li, Gang
    Xu, Dongxin
    Sun, Jinju
    Zhao, Shiyun
    Zheng, Dan
    ADVANCES IN CLINICAL AND EXPERIMENTAL MEDICINE, 2020, 29 (11): : 1337 - 1345
  • [8] Circulating microRNA-194 regulates human melanoma cells via PI3K/AKT/FoxO3a and p53/p21 signaling pathway
    Bai, Ming
    Zhang, Mingzi
    Long, Fei
    Yu, Nanze
    Zeng, Ang
    Zhao, Ru
    ONCOLOGY REPORTS, 2017, 37 (05) : 2702 - 2710
  • [9] Evodiamine Inhibits Colorectal Cancer Growth via RTKs Mediated PI3K/AKT/p53 Signaling Pathway
    Zheng, Qiao
    Jing, Shengnan
    Hu, Lin
    Meng, Xiangrui
    JOURNAL OF CANCER, 2024, 15 (08): : 2361 - 2372
  • [10] Targeting PI3K/AKT/mTOR Signaling Pathway in Breast Cancer
    Li, Huayi
    Prever, Lorenzo
    Hirsch, Emilio
    Gulluni, Federico
    CANCERS, 2021, 13 (14)