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Updated: Feb 4, 2026

Radiosensitivity of Cancer Stem Cells in Lung Cancer Cell Lines
Published on: August 21, 2019
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.
Abstract:
Increasing evidence(s) suggests that cancer stem cells (CSC) in tumours contribute to radio-resistance and recurrence. Notch plays an important role in the maintenance of CSC in many cancers including cervical cancer. Previously, we have reported the role of Fused Toes Homolog (FTS) in conferring radioresistance in cervical cancer cells in vitro and human subjects. The present study investigated the regulatory role of FTS in Notch signaling and maintenance of CSC upon irradiation of cervical cancer cells. The expression of Notch1, 2, 3, cleaved Notch1 and its downstream target Hes1, and spheroid formation was increased by irradiation. Silencing of FTS prevented the radiation-induced increase in the expression of Notch signaling molecules and spheroid formation. Immunoprecipitation showed FTS binds Notch1 and Hes1. Also in silico structural analysis identified putative residues responsible for the binding between FTS and Notch1. Spheroid formation and the expression of CSC markers, Nanog, Oct4A and Sox2 were greatly reduced by combining silencing of FTS and radiation. Taken together, these results suggest that FTS is involved in the regulation of irradiation-induced Notch signaling and CSC activation and can be used as a target to increase radiosensitivity in cervical cancer.
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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