MAD2-p31comet 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, p31comet counteracts the function of MAD2 and leads to mitotic checkpoint silence. In this study, we explore the function of MAD2-p31comet axis in malignant glioma cells. Our results showed that disruption of MAD2-p31comet axis by MAD2 knockdown or p31comet overexpression suppressed cell proliferation, survival and migration of glioma, indicating that MAD2-p31comet axis is required for maintaining glioma cells malignancy. It is noted that MAD2 depletion or p31comet 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-p31comet axis may serve as a potential therapeutic target for glioma.