Abstract A68: MCT-1 oncoprotein induces chromosomal aberrations through impairing centrosomal and mitotic-spindle checkpoints.

Abstract

Centrosome amplification and chromosome abnormalities are frequently detected in neoplasia and during tumorigenesis; however, the mechanism underlying these defects is still unclear. We here identify that the translational regulator, MCT-1, is a novel proto-oncoprotein located at the spindle-organizing apparatus. Decrease of cellular MCT-1 level results in intercellular bridging, chromosome mis-congregation, cytokinesis delay, and post-mitotic apoptosis. MCT-1 induction alongside p53 deficiency (MCT-1-p53) synergistically deregulates mitotic checkpoint kinases and induces Cyclin E protein degradation. These are implicated with increased frequency of cytokinesis failure, multi-nucleation, and centrosome amplification in the subsequent cell cycle. Consistent with the incidences of polyploidy and aneuploidy are progressively induced by the continued cell cultivation and further promoted by the disruption of microtubule structure, array CGH analysis confirms that the pronounced chromosome amplifications and deletions occur on MCT-1-p53 cellular background. This is the first demonstration that MCT-1 plays an important role in the regulation of centrosome integrity and mitotic progression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr A68.