Takahiro Kazami (Presenter)
Chiba University Hospital
Authorship: Takahiro Kazami (1), Takeshi Tomonaga (2), Mamoru Satoh (3), Kazuyuki Matsushita (1), Fumio Nomura (3)
(1) Division of Laboratory Medicine, Chiba University Hospital, Chiba, Japan (2) Laboratory of Proteome Research, National Institute of Biomedical Innovation, Health and Nutrition, Osaka, Japan (3) Division of Clinical Mass Spectrometry, Chiba University Hospital, Chiba, Japan
| Short Abstract Most human cancers show chromosomal instability (CIN), but the precise mechanisms remain uncertain. We found that annexin A2 is overexpressed in the nuclei of CIN cells compared to cells with microsatellite instability (MIN). Ectopic annexin A2 expression in MIN cells results in a high level of aneuploidy and induces lagging chromosomes. These results suggest that nuclear accumulation of annexin A2 plays a crucial role in CIN by disrupting centromere function. In addition, we are carrying out a search of chemotherapy sensitive marker of esophageal cancer that involved in chromosomal instability by using the latest proteomic analysis techniques. |
Long Abstract
Most human cancers show chromosomal instability (CIN), but the precise mechanisms remain uncertain. Annexin A2 is frequently overexpressed in human cancers, and its relationship to tumorigensis is poorly understood. We found that annexin A2 is overexpressed in the nuclei of CIN cells compared to cells with microsatellite instability (MIN). Ectopic annexin A2 expression in MIN cells results in a high level of aneuploidy and induces lagging chromosomes; suppression of annexin A2 in CIN cells reduces such CIN signatures with apoptosis of highly aneuploid cells. Ectopic expression of annexin A2 in MIN cells reduces the expression of centromere proteins. Conversely, annexin A2 knockdown in CIN cells increases the expression of centromere proteins. Moreover, the endogenous expression levels of centromere proteins in CIN cells were greatly reduced compared to MIN cell lines. The reduced expression of centromere proteins likely occurred due to aberrant centromere localization of coilin. These results suggest that nuclear accumulation of annexin A2 plays a crucial role in CIN by disrupting centromere function (Oncogene 34, 4177-89, 2015).@Detailed mechanism of decreased CENP proteins will be discussed. In addition, we are carrying out a search of chemotherapy sensitive marker of esophageal cancer that involved in chromosomal instability by using the latest proteomic analysis techniques.
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