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TTK inhibitor promotes radiosensitivity of liver cancer cells through p21

Haibo Zhang1, Weiping Yao2, Minjun Zhang2

  • 1Department of Radiation Oncology, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, 310014, PR China.

Biochemical and Biophysical Research Communications
|March 10, 2021
PubMed

Insights

Inhibiting the TTK protein kinase (TTK) enhances liver cancer cell sensitivity to radiation therapy. This TTK inhibition promotes DNA damage and apoptosis, suggesting TTK inhibitors as potential radiosensitizers for liver cancer patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Radiotherapy

Background:

  • The serine/threonine kinase TTK (monopolar spindle 1) is crucial for spindle assembly checkpoint signaling.
  • Elevated TTK expression is observed in liver cancer tissues and correlates with poorer patient survival.

Purpose of the Study:

  • To investigate the relationship between TTK inhibition and radiosensitivity in liver cancer.
  • To elucidate the underlying mechanisms by which TTK inhibition affects radiation response.

Main Methods:

  • Analysis of TTK expression in liver cancer tissues and patient survival data.
  • Treatment of liver cancer cells with the TTK inhibitor AZ3146 and radiation.
  • Assessment of cell cycle progression, DNA damage (γ-H2AX foci), apoptosis, necrosis, and centrosome abnormalities.

Main Results:

  • TTK inhibition caused G2/M phase arrest, increased DNA damage, apoptosis, and necrosis in liver cancer cells exposed to radiation.
  • TTK inhibition exacerbated radiation-induced mitotic catastrophe via p21-mediated cell-cycle regulation and centrosome abnormalities.
  • Low TTK expression was associated with improved overall survival in liver cancer patients.

Conclusions:

  • TTK inhibition significantly sensitizes liver cancer cells to radiation therapy in vitro.
  • The mechanism involves p21-mediated cell-cycle regulation, leading to enhanced DNA damage and mitotic catastrophe.
  • TTK inhibitors represent a promising strategy to improve radiosensitivity in liver cancer treatment.
Keywords:
Cell cycleLiver cancerRadiationTTKp21

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