TTK is a potential therapeutic target for cisplatin-resistant ovarian cancer

Yixuan Liu,Keyu Zhu,Renquan Lu,Ying Tong,Hui Zheng,Suhong Xie,Xiaolin Guan,Yanchun Wang,Lin Guo

doi:10.1186/s13048-021-00884-z

Abstract

BackgroundDrug 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.ResultsTTK 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.ConclusionsOur study revealed that TTK may be a promising therapeutic target for cisplatin-resistant ovarian cancer.

Highlights

Ovarian cancer is one of the most common lethal gynecologic malignancy with the third morbidity rate and the first mortality rate
Threonine and tyrosine kinase (TTK) was up‐regulated in cisplatin‐resistant ovarian cancer cell line Cisplatin-resistant A2780 cell line was induced through continuous stimulation with cisplatin in vitro
The inhibitor of TTK or PI3K could significantly suppress the activation of the PI3K/AKT pathway and enhanced the cisplatin sensitivity of A2780cis cells (Fig. 4C, D). These results proved that TTK facilitated proliferation of cisplatin-resistant cells by activating PI3K/AKT signaling pathway

Summary

Introduction

Ovarian cancer is one of the most common lethal gynecologic malignancy with the third morbidity rate and the first mortality rate. The 5 years survival rate after early surgery is up to 80-90, 70% of the patients still have poor prognosis because it is usually diagnosed at advanced stages [2]. Surgery combined with cisplatin chemotherapy is the main treatment for malignant ovarian tumors. Threonine and tyrosine kinase (TTK), an integral part of the spindle assembly checkpoint, works as a monitor mechanism for ensuring chromosomal separation [5]. 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. 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

Methods

Results

Discussion

Conclusion