Institute of Bioinformatics and Biosignal Transduction, National Cheng Kung University, Tainan, Taiwan, Republic of China.
J Pathol. 2011 Oct;225(2):243-54. doi: 10.1002/path.2934. Epub 2011 Jun 27.
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.
AURKC 的过表达已在人类结直肠癌、甲状腺癌和几种癌细胞系中被检测到。然而，在癌细胞中过表达 AURKC 的调节和临床意义尚不清楚。在这里，我们发现 AURKC 的升高会增加癌细胞的增殖、转化和迁移。重要的是，AURKC 的激酶活性是这些肿瘤相关特性所必需的。对人类癌症标本的分析表明，AURKC 在宫颈癌中的表达增加，并且与结直肠癌的分期高度相关。过表达的 AURKC-GFP 定位于有丝分裂染色体的着丝粒区域，导致 AURKB 的水平降低，AURKB 是纺锤体检验点的关键调节剂。转录抑制因子 PLZF 通过募集到其启动子区域，下调 AURKC 的表达。PLZF 和 AURKC mRNA 的表达水平在人宫颈癌和结直肠癌中呈现相反的模式。总之，我们的结果为具有 AURKC 表达的人类癌症提供了重要的见解，这可能成为未来癌症治疗的潜在靶点。
