Translational up-regulation of Aurora-A in EGFR-overexpressed cancer

Chien Hsien Lai, Joseph T. Tseng, Yi Chao Lee, Ying Ju Chen, Jeng Chang Lee, Bo Wen Lin, Tai Chien Huang, Yao Wen Liu, Tzeng Horng Leu, Yi Wen Liu, Ya Ping Chen, Wen Chang Chang, Liang Yi Hung

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15 引文 斯高帕斯(Scopus)

摘要

Abnormal expression of Aurora-A and epidermal growth factor receptor (EGFR) is observed in different kinds of cancer and associated with poor prognosis in cancer patients. However, the relationship between Aurora-A and EGFR in tumour development was not clear. In previous reports, we found that EGFR translocates to nucleus to activate Aurora-A expression after EGF treatment in EGFR-overexpressed cells. However, we also observed that not all the EGFR-overexpressed cells have the nuclear EGFR pathway to mediate the Aurora-A expression. In this study, we demonstrated that EGF signalling increased the Aurora-A protein expression in EGFR-overexpressed colorectal cancer cell lines via increasing the translational efficiency. In addition, the overexpression of EGFR was also associated with higher expression of Aurora-A in clinical colorectal samples. Activation of the PI3K/Akt/mTOR and MEK/ERK pathways mediated the effect of EGF-induced translational up-regulation. Besides, only the splicing variants containing exon 2 of Aurora-A mRNA showed increased interaction with the translational complex to synthesize Aurora-A protein under EGF stimulus. Besides, the exon 2 containing splicing variants were the major Aurora-A splicing forms expressed in human colorectal cancers. Taken together, our results propose a novel regulatory mechanism for the abnormal expression of Aurora-A in EGFR-overexpressed cancers, and highlight the importance of alternative 5'-UTR splicing variants in regulating Aurora-A expression. Furthermore, the specific expression of exon 2 containing splicing variants in cancer tissues may serve as a potential target for cancer therapy in the future.

原文英語
頁(從 - 到)1520-1531
頁數12
期刊Journal of Cellular and Molecular Medicine
14
發行號6 B
DOIs
出版狀態已發佈 - 六月 2010
對外發佈

ASJC Scopus subject areas

  • 細胞生物學
  • 分子醫學

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