Ataxin-1 regulates epithelial-mesenchymal transition of cervical cancer cells

A. Ram Kang, Hyoung Tae An, Jesang Ko, Seongman Kang

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

The mutant form of the protein ataxin-1 (ATXN1) causes the neurodegenerative disease spinocerebellar ataxia type-1. Recently, ATXN1 was reported to enhance E-cadherin expression in the breast cancer cell line MCF-7, suggesting a potential association between ATXN1 and cancer development. In the present study, we discovered a novel mechanism through which ATXN1 regulates the epithelial- mesenchymal transition (EMT) of cancer cells. Hypoxia-induced upregulation of the Notch intracellular domain expression decreased ATXN1 expression via MDM2-associated ubiquitination and degradation. In cervical cancer cells, ATXN1 knockdown induced EMT by directly regulating Snail expression, leading to matrix metalloproteinase activation and the promotion of cell migration and invasion. These findings provide insights into a novel mechanism of tumorigenesis and will facilitate the development of new and more effective therapies for cancer.

Original languageEnglish
Pages (from-to)18248-18259
Number of pages12
JournalOncotarget
Volume8
Issue number11
DOIs
Publication statusPublished - 2017

Keywords

  • ATXN1
  • Cervical cancer
  • Epithelial-mesenchymal transition
  • Notch intracellular domain

ASJC Scopus subject areas

  • Oncology

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