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

• Published in: Biochemical and biophysical research communications Vol. 507; no. 1-4; pp. 74 - 82
• Main Authors: Chen, Miaomiao, Zhang, Hongqin, Zhang, Guihong, Zhong, Ailing, Ma, Qian, Kai, Jinyan, Tong, Yin, Xie, Suhong, Wang, Yanchun, Zheng, Hui, Guo, Lin, Lu, Renquan
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 09.12.2018
• Subjects: 60 APPLIED LIFE SCIENCES; AKT signaling pathway; apoptosis; Breast cancer; breast neoplasms; breasts; CARCINOMAS; Cell apoptosis; CELL PROLIFERATION; disease course; gene expression; genes; humans; in vitro studies; MAMMARY GLANDS; microarray technology; MICROTUBULES; MITOSIS; neoplasm cells; p53; phosphatidylinositol 3-kinase; phosphorylation; RNA; signal transduction; therapeutics; tissues; TPX2; Xenopus; TPX2; Breast cancer; AKT signaling pathway; Cell apoptosis; p53
• ISSN: 0006-291X; 1090-2104; 1090-2104
• DOI: 10.1016/j.bbrc.2018.10.164

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. [Display omitted] •TPX2 expression is frequently upregulated in breast carcinoma and associates with the progression of breast cancer.•TPX2 regulates proliferation and cell apoptosis in breast cancer cells.•TPX2 regulates proliferation and cell apoptosis through PI3K/AKT/P21 signaling pathway.•TPX2 interacts with P53 and MDM2 to regulate cell apoptosis.