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.

View at publisher (open access)

Abstract

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.

Impact and interest:

5 citations in Scopus
Search Google Scholar™

Citation counts are sourced monthly from Scopus and Web of Science® citation databases.

These databases contain citations from different subsets of available publications and different time periods and thus the citation count from each is usually different. Some works are not in either database and no count is displayed. Scopus includes citations from articles published in 1996 onwards, and Web of Science® generally from 1980 onwards.

Citations counts from the Google Scholar™ indexing service can be viewed at the linked Google Scholar™ search.

Full-text downloads:

14 since deposited on 31 Jul 2016
14 in the past twelve months

Full-text downloads displays the total number of times this work’s files (e.g., a PDF) have been downloaded from QUT ePrints as well as the number of downloads in the previous 365 days. The count includes downloads for all files if a work has more than one.

ID Code: 97702
Item Type: Journal Article
Refereed: Yes
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
DOI: 10.18632/oncotarget.2696
ISSN: 1949-2553
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

Export: EndNote | Dublin Core | BibTeX

Repository Staff Only: item control page