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Background: Drug resistance and recurrence are main contributors to the poor prognosis of ovarian cancer. Cisplatin is a platinum compound which is widely used in the treatment of various solid tumors including ovarian cancer. Up to now, the mechanism of cisplatin resistance in ovarian cancer is unclear. Threonine and tyrosine kinase (TTK), an integral part of the spindle assembly checkpoint, may be a potential new target associated with chemotherapy sensitivity. Results: TTK was up-regulated in the cisplatin-resistant ovarian cancer cell line. Down-regulation of TTK could recover the sensitivity of cisplatin-resistant ovarian cancer cells to cisplatin treatment. Mechanistically, the PI3K/AKT signaling pathway was activated in cisplatin-resistant cells, and this pathway would be affected by TTK expression. Furthermore, TTK was highly expressed in the tissues of ovarian cancer patients, especially those acquired resistance to cisplatin. Conclusions: Our study revealed that TTK may be a promising therapeutic target for cisplatin-resistant ovarian cancer. [ABSTRACT FROM AUTHOR]

Abstract 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. Graphical abstract Image 1 Highlights • 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. [ABSTRACT FROM AUTHOR]