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Roles of 14-3-3η in mitotic progression and its potential use as a therapeutic target for cancers

Oncogene volume 32, pages 1560–1569 (2013)Cite this article

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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.

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Acknowledgements

We thank Ye Won Lee, Dr Jung Ki Kim, Min Young Kim and Min Su Ju for administrative support. This study was supported by National Research Foundation grant funded by the Korea government (MEST) (2011-0030833 and 2010-0007555), a grant from National R and D Program for Cancer Control, Ministry of Health and Welfare, Republic of Korea (0920290) and National R and D Program through the Dong-nam Institute of Radiological and Medical Sciences (DIRAMS) funded by the Ministry of Education, Science and Technology (50593-2011, 50594-2011 and 50597-2012).

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  1. C G Lee and G-Y Park: These authors contributed equally to this work.

Authors and Affiliations

  1. Research Center, Dongnam Institute of Radiological and Medical Sciences, Busan, Korea

    C G Lee, G-Y Park, Y K Han, J H Lee, S H Chun, Y-J Choi & K Yang

  2. Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Korea

    C G Lee, H-Y Park, K-H Lim, E-G Kim & C-W Lee

  3. Center for Molecular Medicine, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Korea

    C G Lee & C-W Lee

  4. Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Suwon, Korea

    C-W Lee

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Lee, C., Park, GY., Han, Y. et al. Roles of 14-3-3η in mitotic progression and its potential use as a therapeutic target for cancers. Oncogene 32, 1560–1569 (2013). https://doi.org/10.1038/onc.2012.170

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