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

Area of Science:

• * Molecular Biology
• * Cancer Research
• * Genetics

Background:

• * Metastasis is the primary cause of breast cancer mortality.
• * Epithelial-to-mesenchymal transition (EMT) is crucial for cancer cell spread.
• * Long non-coding RNAs (lncRNAs) are increasingly recognized for their role in tumor progression.

Purpose of the Study:

• * To identify novel lncRNAs involved in TGFβ-induced EMT in breast cancer.
• * To investigate the function and mechanism of a specific lncRNA, ET-20, in EMT and metastasis.
• * To explore the therapeutic potential of targeting ET-20 for breast cancer treatment.

Main Methods:

• * Identified 114 novel EMT-associated transcripts (ETs) in murine breast cancer cells.
• * Characterized the ET-20 gene locus and its relationship with the tenascin C (Tnc) gene.
• * Investigated the regulatory role of Sox4 on ET-20 and Tnc expression.
• * Performed experiments to assess the impact of ET-20 ablation on Tnc expression and EMT.
• * Analyzed the interaction of ET-20 with desmosomal proteins.
• * Examined the expression of ET-20 variants in human invasive breast cancer cell lines.

Main Results:

• * Identified 114 novel lncRNAs (ETs) differentially expressed during EMT.
• * Discovered that ET-20, a lncRNA within the Tnc locus, is regulated by Sox4.
• * Demonstrated that ET-20 ablation significantly inhibits Tnc expression and EMT.
• * Revealed that ET-20 promotes EMT by interacting with desmosomal proteins and impairing epithelial desmosomes.
• * Found an upregulated short variant of ET-20 in invasive human breast cancer cells, which also promotes EMT.

Conclusions:

• * ET-20 is a critical regulator of EMT and metastasis in breast cancer.
• * Targeting ET-20 offers a promising therapeutic strategy to inhibit cancer spread.
• * ET-20 may serve as a valuable biomarker for identifying invasive breast cancer.