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Translational up-regulation of Aurora-A in EGFR-overexpressed cancer
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...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Blackwell Publishing Ltd
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3829018/ https://www.ncbi.nlm.nih.gov/pubmed/19799648 http://dx.doi.org/10.1111/j.1582-4934.2009.00919.x |
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author | Lai, Chien-Hsien Tseng, Joseph T Lee, Yi-Chao Chen, Ying-Ju Lee, Jeng-Chang Lin, Bo-Wen Huang, Tai-Chien Liu, Yao-Wen Leu, Tzeng-Horng Liu, Yi-Wen Chen, Ya-Ping Chang, Wen-Chang Hung, Liang-Yi |
author_facet | Lai, Chien-Hsien Tseng, Joseph T Lee, Yi-Chao Chen, Ying-Ju Lee, Jeng-Chang Lin, Bo-Wen Huang, Tai-Chien Liu, Yao-Wen Leu, Tzeng-Horng Liu, Yi-Wen Chen, Ya-Ping Chang, Wen-Chang Hung, Liang-Yi |
author_sort | Lai, Chien-Hsien |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3829018 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | Blackwell Publishing Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-38290182015-04-20 Translational up-regulation of Aurora-A in EGFR-overexpressed cancer Lai, Chien-Hsien Tseng, Joseph T Lee, Yi-Chao Chen, Ying-Ju Lee, Jeng-Chang Lin, Bo-Wen Huang, Tai-Chien Liu, Yao-Wen Leu, Tzeng-Horng Liu, Yi-Wen Chen, Ya-Ping Chang, Wen-Chang Hung, Liang-Yi J Cell Mol Med Original Articles 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. Blackwell Publishing Ltd 2010-06 2009-10-03 /pmc/articles/PMC3829018/ /pubmed/19799648 http://dx.doi.org/10.1111/j.1582-4934.2009.00919.x Text en © 2009 The Authors Journal compilation © 2010 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd |
spellingShingle | Original Articles Lai, Chien-Hsien Tseng, Joseph T Lee, Yi-Chao Chen, Ying-Ju Lee, Jeng-Chang Lin, Bo-Wen Huang, Tai-Chien Liu, Yao-Wen Leu, Tzeng-Horng Liu, Yi-Wen Chen, Ya-Ping Chang, Wen-Chang Hung, Liang-Yi Translational up-regulation of Aurora-A in EGFR-overexpressed cancer |
title | Translational up-regulation of Aurora-A in EGFR-overexpressed cancer |
title_full | Translational up-regulation of Aurora-A in EGFR-overexpressed cancer |
title_fullStr | Translational up-regulation of Aurora-A in EGFR-overexpressed cancer |
title_full_unstemmed | Translational up-regulation of Aurora-A in EGFR-overexpressed cancer |
title_short | Translational up-regulation of Aurora-A in EGFR-overexpressed cancer |
title_sort | translational up-regulation of aurora-a in egfr-overexpressed cancer |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3829018/ https://www.ncbi.nlm.nih.gov/pubmed/19799648 http://dx.doi.org/10.1111/j.1582-4934.2009.00919.x |
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