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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.

Author information

Prabakaran DS1, Muthusami S2, Sivaraman T3, Yu JR4, Park WY5.
1
Department of Radiation Oncology, Chungbuk National University College of Medicine, Cheongju 28644, Republic of Korea.
2
Department of Biochemistry, Karpagam Academy of Higher Education, Eachanari, Coimbatore 641 021, Tamilnadu, India.
3
Department of Biotechnology, Karpagam Academy of Higher Education, Eachanari, Coimbatore 641 021, Tamilnadu, India.
4
Department of Environmental and Tropical Medicine, Konkuk University College of Medicine, Chungju 27478, Republic of Korea.
5
Department of Radiation Oncology, Chungbuk National University College of Medicine, Cheongju 28644, Republic of Korea. Electronic address: wynpark@chungbuk.ac.kr.