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

A. Ram Kang, Hyoung Tae An, Jesang Ko, Eui Ju Choi, Seongman Kang

    Research output: Contribution to journalArticlepeer-review

    20 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

    Bibliographical note

    Funding Information:
    National Research Foundation of Korea (NRF) grant (MEST) (2015R1A2A2A01003516) National R&D Program for Cancer Control, the Ministry of Health & Welfare, Republic of Korea (1320010). National Research Foundation of Korea (NRF) grant (2015R1A4A1041919).

    Publisher Copyright:
    © Kang et al.

    Keywords

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

    ASJC Scopus subject areas

    • Oncology

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