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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 2010
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.
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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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