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Ataxin-1 is involved in tumorigenesis of cervical cancer cells via the EGFR–RAS–MAPK signaling pathway

Ataxin-1 (ATXN1) is a coregulator protein within which expansion of the polyglutamine tract causes spinocerebellar ataxia type 1, an autosomal dominant neurodegenerative disorder. Previously, we reported that ATXN1 regulates the epithelial–mesenchymal transition of cervical cancer cells. In the pres...

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Autores principales: Kang, A-Ram, An, Hyoung-Tae, Ko, Jesang, Choi, Eui-Ju, Kang, Seongman
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5706899/
https://www.ncbi.nlm.nih.gov/pubmed/29212253
http://dx.doi.org/10.18632/oncotarget.21814
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author Kang, A-Ram
An, Hyoung-Tae
Ko, Jesang
Choi, Eui-Ju
Kang, Seongman
author_facet Kang, A-Ram
An, Hyoung-Tae
Ko, Jesang
Choi, Eui-Ju
Kang, Seongman
author_sort Kang, A-Ram
collection PubMed
description Ataxin-1 (ATXN1) is a coregulator protein within which expansion of the polyglutamine tract causes spinocerebellar ataxia type 1, an autosomal dominant neurodegenerative disorder. Previously, we reported that ATXN1 regulates the epithelial–mesenchymal transition of cervical cancer cells. In the present study, we demonstrate that ATXN1 is involved in cervical cancer tumorigenesis by promoting the proliferation of human cervical cancer cells. Chromatin immunoprecipitation assays showed that ATXN1 bound to the promoter region within cyclin D1 and activated cyclin D1 transcription, resulting in cell proliferation. ATXN1 promoted cyclin D1 expression through the EGFR–RAS–MAPK signaling pathway. Mouse xenograft tumorigenicity assays showed that ATXN1 downregulation inhibited tumorigenesis in cervical cancer cell lines in nude mice. Human cervical cancer tissue microarrays and immunohistochemical techniques showed that ATXN1 was significantly upregulated in many such tissues. Our results suggest that ATXN1 plays an important role in cervical cancer tumorigenesis and is a prognostic marker for cervical cancer.
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spelling pubmed-57068992017-12-05 Ataxin-1 is involved in tumorigenesis of cervical cancer cells via the EGFR–RAS–MAPK signaling pathway Kang, A-Ram An, Hyoung-Tae Ko, Jesang Choi, Eui-Ju Kang, Seongman Oncotarget Research Paper Ataxin-1 (ATXN1) is a coregulator protein within which expansion of the polyglutamine tract causes spinocerebellar ataxia type 1, an autosomal dominant neurodegenerative disorder. Previously, we reported that ATXN1 regulates the epithelial–mesenchymal transition of cervical cancer cells. In the present study, we demonstrate that ATXN1 is involved in cervical cancer tumorigenesis by promoting the proliferation of human cervical cancer cells. Chromatin immunoprecipitation assays showed that ATXN1 bound to the promoter region within cyclin D1 and activated cyclin D1 transcription, resulting in cell proliferation. ATXN1 promoted cyclin D1 expression through the EGFR–RAS–MAPK signaling pathway. Mouse xenograft tumorigenicity assays showed that ATXN1 downregulation inhibited tumorigenesis in cervical cancer cell lines in nude mice. Human cervical cancer tissue microarrays and immunohistochemical techniques showed that ATXN1 was significantly upregulated in many such tissues. Our results suggest that ATXN1 plays an important role in cervical cancer tumorigenesis and is a prognostic marker for cervical cancer. Impact Journals LLC 2017-10-10 /pmc/articles/PMC5706899/ /pubmed/29212253 http://dx.doi.org/10.18632/oncotarget.21814 Text en Copyright: © 2017 Kang et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Kang, A-Ram
An, Hyoung-Tae
Ko, Jesang
Choi, Eui-Ju
Kang, Seongman
Ataxin-1 is involved in tumorigenesis of cervical cancer cells via the EGFR–RAS–MAPK signaling pathway
title Ataxin-1 is involved in tumorigenesis of cervical cancer cells via the EGFR–RAS–MAPK signaling pathway
title_full Ataxin-1 is involved in tumorigenesis of cervical cancer cells via the EGFR–RAS–MAPK signaling pathway
title_fullStr Ataxin-1 is involved in tumorigenesis of cervical cancer cells via the EGFR–RAS–MAPK signaling pathway
title_full_unstemmed Ataxin-1 is involved in tumorigenesis of cervical cancer cells via the EGFR–RAS–MAPK signaling pathway
title_short Ataxin-1 is involved in tumorigenesis of cervical cancer cells via the EGFR–RAS–MAPK signaling pathway
title_sort ataxin-1 is involved in tumorigenesis of cervical cancer cells via the egfr–ras–mapk signaling pathway
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5706899/
https://www.ncbi.nlm.nih.gov/pubmed/29212253
http://dx.doi.org/10.18632/oncotarget.21814
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