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

Oncogene
C G LeeC-W Lee

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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Citations

Oct 17, 2013·Carcinogenesis·Tae Woo KimKyung Chan Park
Jan 21, 2014·Connective Tissue Research·William G Stetler-Stevenson, Noah Veis Gavil
Nov 3, 2015·Scientific Reports·Jeong Yoon HanChang Geun Lee
Jan 11, 2020·Journal of Cellular Biochemistry·Elżbieta BoratynHanna Rokita
Dec 29, 2016·Oncotarget·Verónica CánovasRosanna Paciucci

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