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- Title
Roles of 14-3-3η in mitotic progression and its potential use as a therapeutic target for cancers.
- Authors
Lee, C G; Park, G-Y; Han, Y K; Lee, J H; Chun, S H; Park, H-Y; Lim, K-H; Kim, E-G; Choi, Y-J; Yang, K; Lee, C-W
- 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.
- Subjects
14-3-3 proteins; MITOSIS; CANCER treatment; CELL death; ANTINEOPLASTIC agents; ANTIMITOTIC agents; MICROTUBULES; ANEUPLOIDY
- Publication
Oncogene, 2013, Vol 32, Issue 12, p1560
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/onc.2012.170