Oncotarget

Research Papers:

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

A-ram Kang, Hyoung-Tae An, Jesang Ko and Seongman Kang _

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Oncotarget. 2017; 8:18248-18259. https://doi.org/10.18632/oncotarget.15319

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Abstract

A-Ram Kang1, Hyoung-Tae An1, Jesang Ko1, Seongman Kang1

1Division of Life Sciences, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Korea

Correspondence to:

Seongman Kang, email: skang@korea.ac.kr

Keywords: ATXN1, cervical cancer, epithelial–mesenchymal transition, notch intracellular domain

Received: October 31, 2016    Accepted: December 21, 2016    Published: February 14, 2017

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.


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