期刊
MOLECULAR CARCINOGENESIS
卷 48, 期 9, 页码 810-820出版社
WILEY-LISS
DOI: 10.1002/mc.20525
关键词
kinase; STK15; head and neck cancer; centrosome; transformation
资金
- Hiroshima Prefectural University Specially Promoted Research Grant [H-20]
- Ministry of Education, Science, Sports and Culture [19656250]
Aurora-A, also known as Aik, BTAK, or STK15, is a centrosomal serine/threonine protein kinase, which is protooncogenic and is overexpressed in a wide range of human cancers. Besides gene amplification and mRNA overexpression, proteolytic resistance mechanisms are thought to contribute to overexpression of Aurora-A. However, it is not yet clear how overexpressed Aurora-A affects the expression of transformed phenotype. Here, we found that nuclear accumulation of Aurora-A was critical for transformation activity. Cellular protein fractionation experiments and immunoblot analysis demonstrated a predominance of Aurora-A in the nuclear soluble fraction in head and neck cancer cells. Indirect immunofluorescence using confocal laser microscopy confirmed nuclear Aurora-A in head and neck cancer cells, while most oral keratinocytes exhibited only centrosomal localization. The expression of nuclear export signal-fused Aurora-A demonstrated that the oncogenic transformation activity was lost on disruption of the nuclear localization. Thus, the cytoplasmic localization of overexpressed Aurora-A previously demonstrated by immunohistochemical analysis is not likely to correspond to that in intact cancer cells. This study identifies an alternative mode of Aurora-A overexpression in cancer, through nuclear rather than cytoplasmic functions. We suggest that substrates of Aurora-A in the cell nuclear soluble fraction can represent a novel therapeutic target for cancer. (C) 2009 Wiley-Liss, Inc.
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