title: The involvement of MCT-1 oncoprotein in inducing mitotic catastrophe and nuclear abnormalities.
abstract: Centrosome amplification and chromosome abnormality are frequently identified in neoplasia and tumorigenesis. However, the mechanisms underlying these defects remain unclear. We here identify that MCT-1 is a centrosomal oncoprotein involved in mitosis. Knockdown of MCT-1 protein results in intercellular bridging, chromosome mis-congregation, cytokinesis delay, and mitotic death. Introduction of MCT-1 oncogene into the p53 deficient cells (MCT-1-p53), the mitotic checkpoint kinases and proteins are deregulated synergistically. These biochemical alterations are accompanied with increased frequencies of cytokinesis failure, multi-nucleation, and centrosome amplification in subsequent cell cycle. As a result, the incidences of polyploidy and aneuploidy are progressively induced by prolonged cell cultivation or further promoted by sustained spindle damage on MCT-1-p53 background. These data show that the oncoprotein perturbs centrosome structure and mitotic progression, which provide the molecular aspect of chromsomal abnormality in vitro and the information for understanding the stepwise progression of tumors under oncogenic stress.
authors.affiliation: Institute of Molecular and Genomic Medicine, National Health Research Institutes, Miaoli, Taiwan.
authors.forename: Hung-Ju
authors.initials: HJ
authors.lastname: Shih
authors.forename: Kang-Lin
authors.initials: KL
authors.lastname: Chu
authors.forename: Meng-Hsun
authors.initials: MH
authors.lastname: Wu
authors.forename: Pei-Hsuan
authors.initials: PH
authors.lastname: Wu
authors.forename: Wei-Wen
authors.initials: WW
authors.lastname: Chang
authors.forename: Jan-Show
authors.initials: JS
authors.lastname: Chu
authors.forename: Lily Hui-Ching
authors.initials: LH
authors.lastname: Wang
authors.forename: Hideki
authors.initials: H
authors.lastname: Takeuchi
authors.forename: Toru
authors.initials: T
authors.lastname: Ouchi
authors.forename: Hsin-Ling
authors.initials: HL
authors.lastname: Hsu
mesh_terms: D000782:Aneuploidy; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D018385:Centrosome / Q000378:metabolism; D048749:Cytokinesis; D006801:Humans; D008938:Mitosis; D015513:Oncogene Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011123:Polyploidy; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; C115081:MCTS1 protein, human; D015513:Oncogene Proteins; D034741:RNA, Small Interfering; D016159:Tumor Suppressor Protein p53