title: Ataxin-1 regulates epithelial-mesenchymal transition of cervical cancer cells.
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.
authors.affiliation: Division of Life Sciences, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Korea.
authors.forename: A-Ram
authors.initials: AR
authors.lastname: Kang
authors.affiliation: Division of Life Sciences, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Korea.
authors.forename: Hyoung-Tae
authors.initials: HT
authors.lastname: An
authors.affiliation: Division of Life Sciences, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Korea.
authors.forename: Jesang
authors.initials: J
authors.lastname: Ko
authors.affiliation: Division of Life Sciences, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Korea.
authors.forename: Seongman
authors.initials: S
authors.lastname: Kang
mesh_terms: D000067696:Ataxin-1 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D015687:Cell Hypoxia / Q000502:physiology; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D020782:Matrix Metalloproteinases / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D051736:Proto-Oncogene Proteins c-mdm2 / Q000378:metabolism; D015398:Signal Transduction; D000071250:Snail Family Transcription Factors / Q000096:biosynthesis; D014162:Transfection; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*
chemical_list: C000593749:ATXN1 protein, human; D000067696:Ataxin-1; C428808:CRCT1 protein, human; D011506:Proteins; D000071250:Snail Family Transcription Factors; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D020782:Matrix Metalloproteinases
keywords: ATXN1; Notch intracellular domain; cervical cancer; epithelial–mesenchymal transition