title: 14-3-3 eta depletion sensitizes glioblastoma cells to irradiation due to enhanced mitotic cell death.
abstract: 14-3-3 proteins have important roles in several cellular processes such as cell cycle progression, the DNA-damage checkpoint and apoptosis. We have shown previously that depleting 14-3-3η, a 14-3-3 isoform, enhances mitotic cell death, and that combining it with microtubule agents is more effective for anticancer therapeutics. In this study, we investigated whether depleting 14-3-3η can be combined with radiotherapy to enhance its therapeutic efficacy. We found that depleting 14-3-3η resulted in a synergistic radiosensitizing effect when combined with radiotherapy in several glioblastoma cell lines, where its specific expression and correlation of its expression level with malignancy have been reported. The radiosensitizing effect was associated with enhanced mitotic cell death by 14-3-3η depletion but not with mitotic catastrophe, which is one of the major cell death mechanisms observed in response to irradiation of most solid tumors. These results suggest that 14-3-3η may be a therapeutic target to overcome radioresistance in glioblastoma.
authors.affiliation: 1] Research Center, Dongnam Institute of Radiological & Medical Sciences, Busan, ROK [2] Department of Biological Sciences, Pusan National University, Busan, ROK.
authors.forename: G-Y
authors.initials: GY
authors.lastname: Park
authors.affiliation: Research Center, Dongnam Institute of Radiological & Medical Sciences, Busan, ROK.
authors.forename: J Y
authors.initials: JY
authors.lastname: Han
authors.affiliation: Research Center, Dongnam Institute of Radiological & Medical Sciences, Busan, ROK.
authors.forename: Y K
authors.initials: YK
authors.lastname: Han
authors.affiliation: Research Center, Dongnam Institute of Radiological & Medical Sciences, Busan, ROK.
authors.forename: S D
authors.initials: SD
authors.lastname: Kim
authors.affiliation: Research Center, Dongnam Institute of Radiological & Medical Sciences, Busan, ROK.
authors.forename: J S
authors.initials: JS
authors.lastname: Kim
authors.affiliation: Research Center, Dongnam Institute of Radiological & Medical Sciences, Busan, ROK.
authors.forename: W S
authors.initials: WS
authors.lastname: Jo
authors.affiliation: Research Center, Dongnam Institute of Radiological & Medical Sciences, Busan, ROK.
authors.forename: S H
authors.initials: SH
authors.lastname: Chun
authors.affiliation: Research Center, Dongnam Institute of Radiological & Medical Sciences, Busan, ROK.
authors.forename: D H
authors.initials: DH
authors.lastname: Jeong
authors.affiliation: 1] Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, ROK [2] Center for Molecular Medicine, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, ROK [3] Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Suwon, ROK.
authors.forename: C-W
authors.initials: CW
authors.lastname: Lee
authors.affiliation: 1] Research Center, Dongnam Institute of Radiological & Medical Sciences, Busan, ROK [2] Department of Radiation Oncology, Dongnam Institute of Radiological & Medical Sciences, Busan, ROK [3] Department of Radiation Oncology, Korea Institute of Radiological & Medical Sciences, Seoul, ROK.
authors.forename: K
authors.initials: K
authors.lastname: Yang
authors.affiliation: Research Center, Dongnam Institute of Radiological & Medical Sciences, Busan, ROK.
authors.forename: C G
authors.initials: CG
authors.lastname: Lee
mesh_terms: D048948:14-3-3 Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D017209:Apoptosis / Q000528:radiation effects; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy*; D002453:Cell Cycle / Q000528:radiation effects; D016923:Cell Death / Q000528:radiation effects; D048708:Cell Growth Processes / Q000528:radiation effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000528:radiation effects; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy*; D006367:HeLa Cells; D006801:Humans; D008938:Mitosis / Q000528:radiation effects; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D011836:Radiation Tolerance / Q000502:physiology; D014162:Transfection
chemical_list: D048948:14-3-3 Proteins; D034741:RNA, Small Interfering; C482984:YWHAH protein, human