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

Authors
Kang, A-RamAn, Hyoung-TaeKo, JesangChoi, Eui-JuKang, Seongman
Issue Date
7-11월-2017
Publisher
IMPACT JOURNALS LLC
Keywords
ATXN1; cervical cancer; EGFR-RAS-MAPK pathway; tumorigenesis
Citation
ONCOTARGET, v.8, no.55, pp.94606 - 94618
Indexed
SCIE
SCOPUS
Journal Title
ONCOTARGET
Volume
8
Number
55
Start Page
94606
End Page
94618
URI
https://scholar.korea.ac.kr/handle/2021.sw.korea/81578
DOI
10.18632/oncotarget.21814
ISSN
1949-2553
Abstract
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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