Receptor for Hyaluronan-Mediated Motility Correlates with Centrosome Abnormalities in Multiple Myeloma and Maintains Mitotic Integrity
作者： Jonathan J. Keats , Tony Reiman , Christopher A. Maxwell , Linda M. Pilarski , Andrew R. Belch
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摘要: Elevated expression of receptor for hyaluronan-mediated motility (RHAMM) within ex vivo diagnostic multiple myeloma plasma cells predicts aggressive disease and patient survival. Here, we investigate the relationship between RHAMM centrosomal abnormalities samples. We report that samples contain pervasive structural numerical abnormalities. Structural, but not numerical, strongly correlate with elevated expression. As others have shown excess pericentriolar material associates abnormal mitoses, modeled exogenous overexpression. overexpression in vitro resulted mitotic defects. To elucidate a mechanism RHAMM-mediated spindle defects, further investigated function. localization mirrors targeting protein Xklp2 (TPX2), interacts assembly factors dynein TPX2. Like TPX2, is up-regulated during mitosis. Moreover, inhibition function experiments reveals TPX2 functions converge to maintain integrity after assembly. postulate augmentation human cancers, including myeloma, can directly affect structure potentially modulate apoptotic cell cycle progression pathways.
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