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

A. Ram Kang, Hyoung Tae An, Je Sang Ko, Eui Ju Choi, Seong Man Kang

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)94606-94618
Number of pages13
JournalOncotarget
Volume8
Issue number55
DOIs
Publication statusPublished - 2017 Nov 1

Keywords

  • ATXN1
  • Cervical cancer
  • EGFR-RAS-MAPK pathway
  • Tumorigenesis

ASJC Scopus subject areas

  • Oncology

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