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FOXM1 Contributes to Chemotherapy Sensitivity in Cervical Cancer by Regulating TTK

Qing Tang1, Anli Xu1, Ying Yang1

  • 1Department of Gynecology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, 264000 Yantai, Shandong, China.

Discovery Medicine
|June 5, 2023
PubMed
Abstract

Insights

Forkhead box protein M1 (FOXM1) regulates threonine tyrosine kinase (TTK) and enhances chemotherapy sensitivity in cervical cancer. This finding may improve treatments for advanced cervical cancer by targeting FOXM1 and TTK pathways.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Chemotherapy resistance is a major challenge in advanced cervical cancer treatment.
  • The roles of Forkhead box protein M1 (FOXM1) and threonine tyrosine kinase (TTK) in chemoresistance are known, but their interaction in cervical cancer is unclear.

Purpose of the Study:

  • To investigate the effect of FOXM1 on TTK expression and its subsequent impact on chemotherapy sensitivity in cervical cancer.
  • To elucidate the underlying mechanism of FOXM1-mediated chemoresistance in cervical cancer.

Main Methods:

  • Immunohistochemistry was used to analyze FOXM1 and TTK expression in cervical cancer tissues.
  • Cell lines (SiHa and Hela) were manipulated (lentivirus, siRNA, pcDNA3.1) to alter FOXM1 expression and assess TTK levels.
  • Cells were treated with paclitaxel or cisplatin to evaluate chemotherapy sensitivity, with xenograft models used for in vivo validation.

Main Results:

  • Cervical cancer tissues exhibited high expression of both FOXM1 and TTK.
  • FOXM1 downregulation reduced TTK expression, cell viability, and cell cycle progression.
  • FOXM1 overexpression enhanced cell viability and DNA damage in response to paclitaxel and cisplatin, an effect reversed by a TTK inhibitor.

Conclusions:

  • FOXM1 plays a crucial role in regulating TTK expression in cervical cancer.
  • FOXM1 influences the therapeutic efficacy of cisplatin and paclitaxel, suggesting its potential as a therapeutic target.
Keywords:
cervical cancercisplatinforkhead box protein M1 (FOXM1)paclitaxelthreonine tyrosine kinase (TTK)

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