AI Article Synopsis
- Epithelial cells undergo a process called epithelial-mesenchymal transition (EMT) during cancer progression, but how they maintain their epithelial characteristics is unclear.
- The long noncoding RNA LITATS1 acts as a protective factor in normal epithelial cells, inhibiting EMT in breast and lung cancers and reducing its expression is linked to worse patient outcomes.
- LITATS1 enhances the degradation of the TGF-β type I receptor, dampening TGF-β/SMAD signaling, and its depletion increases cancer cell mobility and EMT, highlighting its role in preserving epithelial integrity.
Article Abstract
Epithelial cells acquire mesenchymal phenotypes through epithelial-mesenchymal transition (EMT) during cancer progression. However, how epithelial cells retain their epithelial traits and prevent malignant transformation is not well understood. Here, we report that the long noncoding RNA LITATS1 (LINC01137, ZC3H12A-DT) is an epithelial gatekeeper in normal epithelial cells and inhibits EMT in breast and non-small cell lung cancer cells. Transcriptome analysis identified LITATS1 as a TGF-β target gene. LITATS1 expression is reduced in lung adenocarcinoma tissues compared with adjacent normal tissues and correlates with a favorable prognosis in breast and non-small cell lung cancer patients. LITATS1 depletion promotes TGF-β-induced EMT, migration, and extravasation in cancer cells. Unbiased pathway analysis demonstrated that LITATS1 knockdown potently and selectively potentiates TGF-β/SMAD signaling. Mechanistically, LITATS1 enhances the polyubiquitination and proteasomal degradation of TGF-β type I receptor (TβRI). LITATS1 interacts with TβRI and the E3 ligase SMURF2, promoting the cytoplasmic retention of SMURF2. Our findings highlight a protective function of LITATS1 in epithelial integrity maintenance through the attenuation of TGF-β/SMAD signaling and EMT.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10183827 | PMC |
| http://dx.doi.org/10.15252/embj.2022112806 | DOI Listing |
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