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

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 ra...

Celý popis

Uloženo v:
Podrobná bibliografie
Vydáno v:International journal of biological macromolecules Ročník 126; s. 1318 - 1325
Hlavní autoři: Prabakaran, D.S., Muthusami, Sridhar, Sivaraman, T., Yu, Jae-Ran, Park, Woo-Yoon
Médium: Journal Article
Jazyk:angličtina
Vydáno: Netherlands Elsevier B.V 01.04.2019
Témata:
Cancer stem cells
Cervical cancer
Fused Toes Homolog
humans
irradiation
neoplasm cells
Notch
precipitin tests
Radiation
radiation resistance
stem cells
uterine cervical neoplasms
Fused Toes Homolog
Cancer stem cells
Cervical cancer
Notch
Radiation
ISSN:0141-8130, 1879-0003, 1879-0003
On-line přístup:Získat plný text
Tagy: Přidat tag
Žádné tagy, Buďte první, kdo vytvoří štítek k tomuto záznamu!
Popis
Shrnutí: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.
Bibliografie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0141-8130
1879-0003
1879-0003
DOI:10.1016/j.ijbiomac.2018.09.114