Panoply™ Human TTK Knockdown Stable Cell Line

High-grade serous ovarian cancer (HGSOC) is the most lethal gynecological malignancy. TTK protein kinase (TTK) is a regulator of spindle assembly checkpoint signaling and plays a crucial role in cell cycle control and tumorigenesis in various cancers. Here, researchers observed that TTK expression is upregulated in HGSOC patients. High TTK expression is associated with poor prognosis. Genetic and pharmacological inhibition of TTK suppresses ovarian cancer cell proliferation by disrupting cell cycle progression and increasing apoptosis. TTK silencing further enhances cisplatin sensitivity by activating the mammalian target of rapamycin (mTOR) complex and inhibiting cisplatin-induced autophagy. Furthermore, rapamycin-mediated mTOR inhibition partially attenuated this enhanced sensitivity in TTK knockdown cells. In addition, TTK knockdown increased cisplatin toxicity in vivo by reducing autophagy. These findings suggest that combining TTK inhibitors with cisplatin may improve the efficacy of cisplatin in HGSOC patients with high TTK expression.

To investigate the potential function of TTK in ovarian cancer, researchers knocked down TTK expression in CAOV3 and OV90 cells (Figure 1A). The results showed that ovarian cancer cell proliferation was significantly reduced in TTK knockdown cells (Figure 1B). Colony formation assays demonstrated that the long-term proliferative capacity of TTK-knockdown CAOV3 and OV90 cells was inhibited (Figure 1C). TTK is a serine/threonine kinase that regulates the normal progression of the cell cycle. Researchers analyzed the cell cycle to investigate whether this inhibition of cell proliferation was caused by cell cycle disruption. As shown in Figure 1D, downregulation of TTK expression significantly reduced the number of cells in the G1 phase and increased the number of cells in the G2/M phase. Furthermore, there was an increase in the number of cells in the late G2 phase in TTK-knockdown cells, indicating the occurrence of multinucleation. The number of apoptotic cells also increased after TTK expression was reduced. These results suggest that the loss of the TTK gene significantly inhibits ovarian cancer cell proliferation by disrupting the cell cycle progression.

Figure 1. TTK depletion inhibits ovarian cancer cell proliferation by disturbing cell cycle progression. (Qi G, et al., 2021)