[期刊论文]


The long non-coding RNA ET-20 mediates EMT by impairing desmosomes in breast cancer cells

作   者:
Meera Saxena;Mizue Hisano;Melanie Neutzner;Maren Diepenbruck;Robert Ivanek;Kirti Sharma;Ravi K.R. Kalathur;Thomas R. Bürglin;Salvatore Risoli;Gerhard Christofori;

出版年:暂无

页    码:暂无
出版社:The Company of Biologists


摘   要:

The vast majority of breast cancer-associated deaths are due to metastatic spread of cancer cells, a process aided by epithelial-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 TGFβ-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 extra-cellular matrix protein which 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 found upregulated in invasive human breast cancer cell lines where it also promotes EMT. Targeting ET-20 appears a therapeutically attractive lead to restrain EMT and breast cancer metastasis in addition to its potential utility as a biomarker for invasive breast cancer.



关键字:

Breast cancer;Desmosomes;EMT;Metastasis;Tenascin C;lncRNA


所属期刊
Journal of Cell Science
ISSN: 0021-9533
来自:The Company of Biologists