Abstract 49P
Background
Cancer stem-like cells (CSCs) can be a cause of resistance to chemo/radiotherapy. Notch pathway plays a vital role in maintenance of cancer stemness and its activation leads to disease progression and metastasis. FTS gene was initially identified as one of six genes deleted in a mouse mutant called Fused Toes, due to defects in limb development, and referred as FT1/FTS. However, the function of FTS has not been elucidated well in human. We previously reported that FTS plays an essential role in nuclear phosphorylation of EGFR and repair of DNA damage, and epithelial-mesenchymal transition. In this study, we evaluated the role of FTS in Notch and its downstream proteins.
Methods
Human cervical carcinoma cell lines (ME180, HeLa, SiHa, CasKi) were used. Spheroids were made from singel cell suspension. Silencing of FTS was attained with siRNA. Western blot analysis was done to measure protein expression. Immunoprecipitation was done to see the protein interactions. Immunofluorescence was done to see the intracelluar localization of the proteins.
Results
Protein expression of Notch 1 and Notch 2 was increased by ionizing radiation (IR) in the four cervical cancer cell lines tested. Also the protein expression of cleaved Notch1 and Hes1 was increased by IR and it was reduced by FTS-silencing. Imunoprecipation showed FTS bound to Notch1. Expression of Notch, ɣ-secretase complex and its downstream Hes-1 was increased by IR and it was blocked by FTS-silencing. Furthermore, spheroid formation ability and cancer stem cell markers Nanog, Oct-4A, Sox2 were reduced by FTS-silencing.
Conclusions
Notch-mediated stem cell survival is regulated by FTS in cervical cancer cells. FTS can be a treatment target for Notch-mediated stem cell survival in cervical cancer.
Clinical trial identification
Legal entity responsible for the study
Woo-Yoon Park
Funding
National Research Foundation of Korea
Disclosure
All authors have declared no conflicts of interest.
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