title: Roles of 14-3-3η in mitotic progression and its potential use as a therapeutic target for cancers.
abstract: 14-3-3 proteins are involved in several cellular processes, including the G1/S and G2/M cell cycle transitions. However, their roles during mitosis are not well understood. Here, we showed that depletion of 14-3-3η, a 14-3-3 protein isoform, enhanced mitotic cell death, resulting in sensitization to microtubule inhibitors and inhibition of aneuploidy formation. The enhanced mitotic cell death by depletion of 14-3-3η appeared to be both caspase-dependent and independent. Furthermore, enhanced mitotic cell death and a reduction in aneuploidy following 14-3-3η depletion were independent of the mitotic checkpoint, which is thought to be the primary signaling event in the regulation of the cell death induced by microtubule inhibitors. When 14-3-3η depletion was combined with microtubule inhibitors in HCT116 and U87MG cells, it sensitized both cancer cell lines to microtubule inhibitors. These results collectively suggest that 14-3-3η may be required for mitotic progression and may be considered as a novel anti-cancer strategy in combination with microtubule inhibitors.
authors.affiliation: Research Center, Dongnam Institute of Radiological and Medical Sciences, Busan, Korea. cglee@dirams.re.kr
authors.forename: C G
authors.initials: CG
authors.lastname: Lee
authors.forename: G-Y
authors.initials: GY
authors.lastname: Park
authors.forename: Y K
authors.initials: YK
authors.lastname: Han
authors.forename: J H
authors.initials: JH
authors.lastname: Lee
authors.forename: S H
authors.initials: SH
authors.lastname: Chun
authors.forename: H-Y
authors.initials: HY
authors.lastname: Park
authors.forename: K-H
authors.initials: KH
authors.lastname: Lim
authors.forename: E-G
authors.initials: EG
authors.lastname: Kim
authors.forename: Y-J
authors.initials: YJ
authors.lastname: Choi
authors.forename: K
authors.initials: K
authors.lastname: Yang
authors.forename: C-W
authors.initials: CW
authors.lastname: Lee
mesh_terms: D048948:14-3-3 Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D000782:Aneuploidy; D017209:Apoptosis / Q000187:drug effects; D053453:Caspase 9 / Q000502:physiology; D002455:Cell Division; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000502:physiology; D016195:G2 Phase; D006367:HeLa Cells; D006801:Humans; D008870:Microtubules / Q000187:drug effects; D008938:Mitosis; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015739:Nocodazole / Q000494:pharmacology
chemical_list: D048948:14-3-3 Proteins; C499517:FOXO3 protein, human; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; C482984:YWHAH protein, human; D053453:Caspase 9; D015739:Nocodazole