期刊
JOURNAL OF CELL SCIENCE
卷 134, 期 21, 页码 -出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.258418
关键词
Breast cancer; Desmosomes; EMT; lncRNA; Metastasis; Tenascin C
类别
资金
- SystemsX.ch MTD project MetastasiX [2014/268]
- Swiss National Science Foundation (Schweizerischer Nationalfonds zur Forderung der Wissenschaftlichen Forschung) [310030B_163471]
- Swiss Cancer Research Foundation [KFS-3479-08-2014]
- Krebsliga Beider Basel [KlbB-4469-03-2018]
- Research Funds of the University of Basel
- Swiss National Science Foundation (SNF) [310030B_163471] Funding Source: Swiss National Science Foundation (SNF)
The study identified 114 novel lncRNAs associated with EMT, with ET-20 being regulated by the EMT master transcription factor Sox4 and playing a role in promoting EMT by interacting with desmosomal proteins. ET-20 was found to be upregulated in invasive breast cancer cell lines and targeting it could be a potential therapeutic approach to inhibit EMT and breast cancer metastasis.
The vast majority of breast cancer-associated deaths are due to metastatic spread of cancer cells, a process aided by epithelial-to-mesenchymal transition (EMT). Mounting evidence has indicated that long non-coding RNAs (lncRNAs) also contribute to tumor progression. We report the identification of 114 novel lncRNAs that change their expression during TGF beta-induced EMT in murine breast cancer cells (referred to as EMT-associated transcripts; ETs). Of these, the ET-20 gene localizes in antisense orientation within the tenascin C (Tnc) gene locus. TNC is an extracellular matrix protein that is critical for EMT and metastasis formation. Both ET-20 and Tnc are regulated by the EMT master transcription factor Sox4. Notably, ablation of ET-20 lncRNA effectively blocks Tnc expression and with it EMT. Mechanistically, ET-20 interacts with desmosomal proteins, thereby impairing epithelial desmosomes and promoting EMT. A short transcript variant of ET-20 is shown to be upregulated in invasive human breast cancer cell lines, where it also promotes EMT. Targeting ET-20 appears to be a therapeutically attractive lead to restrain EMT and breast cancer metastasis in addition to its potential utility as a biomarker for invasive breast cancer.
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