MAD2-p31(comet) axis deficiency reduces cell proliferation, migration and sensitivity of microtubule-interfering agents in glioma

Mitotic arrest deficient-like-1 (MAD2, also known as MAD2L1) is thought to be an important spindle assembly checkpoint protein, which ensures accurate chromosome segregation and is closely associated with poor prognosis in many cancer. As a MAD2 binding protein, p31(comet) counteracts the function of MAD2 and leads to mitotic checkpoint silence. In this study, we explore the function of MAD2-p31(comet) axis in malignant glioma cells. Our results showed that disruption of MAD2-p31(comet) axis by comet MAD2 knockdown or p31(comet) overexpression suppressed cell proliferation, survival and migration of glioma, indicating that MAD2-p31(comet) axis is required for maintaining glioma cells malignancy. It is noted that MAD2 depletion or p31(comet) overexpression reduced the sensitivity of glioma cells to microtubule-interfering agents paclitaxel and vinblastine, providing clinical guidance for application of such drugs. Taken together, our findings suggest that MAD2-p31(comet) axis may serve as a potential therapeutic target for glioma. (C) 2018 Published by Elsevier Inc.