Ataxin-1 regulates epithelial-mesenchymal transition of cervical cancer cells.
Ataxin-1 regulates epithelial-mesenchymal transition of cervical cancer cells.
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DOI：
10.18632/oncotarget.15319
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发表时间：
2017-03-14
期刊：
影响因子：
--
通讯作者：
Kang S
中科院分区：
文献类型：
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作者：
Kang AR;An HT;Ko J;Kang S
蛋白质ataxin-1（ATXN 1）的突变形式导致神经退行性疾病脊髓小脑共济失调1型。最近，ATXN 1被报道在乳腺癌细胞系MCF-7中增强E-cadherin表达，表明ATXN 1与癌症发展之间的潜在关联。在本研究中，我们发现了ATXN 1调节癌细胞上皮-间质转化（EMT）的新机制。缺氧诱导的Notch细胞内结构域表达上调通过MDM 2相关的泛素化和降解降低ATXN 1的表达。在宫颈癌细胞中，ATXN 1敲低通过直接调节Snail表达诱导EMT，导致基质金属蛋白酶活化并促进细胞迁移和侵袭。这些发现为肿瘤发生的新机制提供了见解，并将促进新的更有效的癌症治疗方法的开发。
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.