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Aberrantly expressed AURKC enhances the transformation and tumourigenicity of epithelial cells

2011; Volume: 225; Issue: 2 Linguagem: Inglês

10.1002/path.2934

1096-9896

Jen‐Hui Tsou, Kung‐Chao Chang, Pey‐Yi Chang‐Liao, Shuting Yang, Chung‐Ta Lee, Yaping Chen, Yi‐Chao Lee, Bo‐Wen Lin, Jenq‐Chang Lee, Meng‐Ru Shen, Chin‐Kai Chuang, Wen‐Chang Chang, Ju‐Ming Wang, Liang‐Yi Hung,

Cancer-related Molecular Pathways

Over-expression of AURKC has been detected in human colorectal cancers, thyroid carcinoma and several cancer cell lines. However, the regulation and clinical implications of over-expressed AURKC in cancer cells are unclear. Here we show that elevated AURKC increases the proliferation, transformation and migration of cancer cells. Importantly, the kinase activity of AURKC is required for these tumour-associated properties. Analysis of human cancer specimens shows that the expression of AURKC is increased in cervical cancer, and is highly correlated with staging in colorectal cancer. Over-expressed AURKC-GFP localizes to the centromeric regions of mitotic chromosomes and results in a decreased level of AURKB, a key regulator of spindle checkpoint. Expression of AURKC is down-regulated by PLZF, a transcriptional repressor, through recruitment to its promoter region. The expression levels of PLZF and AURKC mRNA display opposite patterns in human cervical and colorectal cancers. Taken together, our results provide important insights into human cancers with AURKC expression, which may serve as a potential target for cancer therapy in the future.