Silencing of FTS increases radiosensitivity by blocking radiation-induced Notch1 activation and spheroid formation in

D S Prabakaran1, Sridhar Muthusami2, T Sivaraman3

  • 1Department of Radiation Oncology, Chungbuk National University College of Medicine, Cheongju 28644, Republic of Korea.

Insights

Fused Toes Homolog (FTS) regulates cancer stem cell (CSC) activation and radioresistance in cervical cancer by influencing Notch signaling. Targeting FTS may enhance radiosensitivity, offering a new therapeutic strategy for cervical cancer patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Cancer stem cells (CSCs) drive tumor radioresistance and recurrence.
  • Notch signaling is crucial for CSC maintenance in various cancers, including cervical cancer.
  • Fused Toes Homolog (FTS) has been linked to radioresistance in cervical cancer.

Purpose of the Study:

  • To investigate the regulatory role of FTS in Notch signaling and CSC maintenance following irradiation of cervical cancer cells.
  • To determine if FTS influences the radiation-induced activation of CSCs.

Main Methods:

  • Irradiation of cervical cancer cells.
  • Quantitative analysis of Notch signaling molecules (Notch1, 2, 3, cleaved Notch1, Hes1) and CSC markers (Nanog, Oct4A, Sox2).
  • FTS silencing using RNA interference.
  • Spheroid formation assays.
  • Immunoprecipitation and in silico structural analysis to assess FTS-Notch1 interaction.

Main Results:

  • Irradiation increased Notch signaling components and spheroid formation, indicating CSC activation.
  • FTS silencing abrogated radiation-induced increases in Notch signaling and spheroid formation.
  • FTS was shown to bind Notch1 and Hes1.
  • Combined FTS silencing and radiation significantly reduced spheroid formation and CSC marker expression.

Conclusions:

  • FTS plays a key role in regulating irradiation-induced Notch signaling and CSC activation in cervical cancer.
  • FTS represents a potential therapeutic target to enhance cervical cancer radiosensitivity.

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