The ubiquitin ligase Siah is a novel regulator of Zeb1 in breast cancer
Chen, Anna, Wong, Christina S.F., Liu, Mira M.C., House, Coline M., Sceneay, Jacyln, Bowtell, David D., Thompson, Erik W., & Möller, Andreas (2015) The ubiquitin ligase Siah is a novel regulator of Zeb1 in breast cancer. Oncotarget, 6(2), pp. 862-873.
Elucidating the mechanisms that underlie metastasis is of paramount importance to understanding tumor progression and to the development of novel therapeutics. Epithelial to Mesenchymal Transition (EMT) plays a vital role in tumor cell dissemination and is regulated by a core cassette of transcription factors. Despite recent advances, the molecular pathways that regulate the EMT program have not yet been fully delineated. We show that Siah ubiquitin ligases regulate Zeb1 protein, a key EMT transcription factor. The induction of EMT in breast cancer cells leads to the down-regulation of Siah, while the loss of Siah induces a mesenchymal phenotype, concurrent with an up-regulation of Zeb1. Overexpression of Siah in vitro mediates Zeb1 degradation, which can be blocked with a Siah peptide inhibitor. Thus, this work demonstrates that Siah is a novel regulator of EMT. This work is the first to identify a mechanism of post-translational regulation of the key Epithelial to Mesenchymal Transition transcription factor Zeb1.
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|Item Type:||Journal Article|
|Keywords:||Animals, Blotting, Western, Breast Neoplasms/genetics/metabolism/pathology, Cell Line, Cell Line, Tumor, Epithelial-Mesenchymal Transition/drug effects/*genetics, Female, Gene Expression Profiling, *Gene Expression Regulation, Neoplastic, Homeodomain Proteins/*genetics/metabolism, Humans, MCF-7 Cells, Mice, Microscopy, Fluorescence, Models, Genetic, Nuclear Proteins/*genetics/metabolism, RNA Interference, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction/drug effects/genetics, Transcription Factors/*genetics/metabolism, Transforming Growth Factor alpha/pharmacology, Transforming Growth Factor beta/pharmacology, Ubiquitin-Protein Ligases/*genetics/metabolism|
|Subjects:||Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000)
Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > ONCOLOGY AND CARCINOGENESIS (111200)
Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > ONCOLOGY AND CARCINOGENESIS (111200) > Cancer Cell Biology (111201)
|Divisions:||Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
|Copyright Owner:||Copyright 2015 The Author(s)|
|Deposited On:||31 Jul 2016 23:32|
|Last Modified:||02 Aug 2016 04:48|
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