TTK is a potential therapeutic target for cisplatin-resistant ovarian cancer
Yixuan Liu, Keyu Zhu, Xiaolin Guan, Suhong Xie, Yanchun Wang, Ying Tong, Lin Guo, Hui Zheng, Renquan Lu
Abstract
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.