China Oncology ›› 2021, Vol. 31 ›› Issue (3): 182-191.doi: 10.19401/j.cnki.1007-3639.2021.03.004

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The function of TTK1 in platinum-resistant ovarian cancer

LIU Yixuan 1 , WEN Zexuan 2 , GUO Lin 1 , LU Renquan #br#   

  1. 1. Department of Clinical Laboratory, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; 2. Department of Epidemiology, School of Public Health, Fudan University, Shanghai 200030, China
  • Online:2021-03-30 Published:2021-04-01
  • Contact: LU Renquan E-mail: lurenquan@126.com

Abstract: Background and purpose: Threonine tyrosine kinase 1 (TTK1) is an integral part of the spindle assembly checkpoint and ensuring the correct separation of chromosomes. TTK1 may be a potential target associated with chemotherapy sensitivity. Ovarian cancer, one of the most common malignant tumors in the female, has the third incidence rate and the first mortality rate among gynecological malignant tumors. Clinically, platinum-containing drugs are commonly used in chemotherapy for ovarian cancer. Patients, however, often develop platinum resistance after long term chemotherapy, which affects their treatment course and prognosis. Therefore, it is necessary to find genes associated with platinum-resistance as effective targets for the treatment of ovarian cancer. The purpose of this study was to investigate the relationship between TTK1 and platinum resistance in ovarian cancer. Methods: The genes interacting with TTK1 were screened out through big data analysis, the biological functions of TTK1 were explored, and a network model of drug resistance mechanisms was established based on the relevant gene functions. Platinum resistance-related pathways in ovarian cancer were analyzed by GEO microarray. The RNA of platinum-resistant ovarian cancer cells with TTK1 knockdown was sequenced to analyze the relationship between TTK1 and drug resistance-related pathways. Results: TTK1 participated in the process of cell mitosis and cell differentiation, and played an important role in the process of chromosome separation. It was found that TTK1 was overexpressed in ovarian cancer patients with platinum resistance, and RNA sequencing results further displayed the signaling pathways associated with TTK1 in platinum-resistant cells of ovarian cancer. Conclusion: TTK1 may participate platinum resistance in ovarian cancer through a variety of pathways, and the combined treatment of ovarian cancer based on TTK1 inhibitors may become a new mode of treatment.

Key words: Threonine tyrosine kinase 1, Ovarian cancer, Platinum