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LncRNA LITATS1 suppresses TGF-ß-induced EMT and cancer cell plasticity by potentiating TßRI degradation.
Fan, Chuannan; Wang, Qian; Kuipers, Thomas B; Cats, Davy; Iyengar, Prasanna Vasudevan; Hagenaars, Sophie C; Mesker, Wilma E; Devilee, Peter; Tollenaar, Rob A E M; Mei, Hailiang; Ten Dijke, Peter.
Afiliação
  • Fan C; Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, The Netherlands.
  • Wang Q; Oncode Institute, Leiden University Medical Center, Leiden, The Netherlands.
  • Kuipers TB; Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, The Netherlands.
  • Cats D; Oncode Institute, Leiden University Medical Center, Leiden, The Netherlands.
  • Iyengar PV; Department of Biomedical Data Sciences, Sequencing Analysis Support Core, Leiden University Medical Center, Leiden, The Netherlands.
  • Hagenaars SC; Department of Biomedical Data Sciences, Sequencing Analysis Support Core, Leiden University Medical Center, Leiden, The Netherlands.
  • Mesker WE; Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, The Netherlands.
  • Devilee P; Oncode Institute, Leiden University Medical Center, Leiden, The Netherlands.
  • Tollenaar RAEM; Department of Surgery, Leiden University Medical Centre, Leiden, The Netherlands.
  • Mei H; Department of Surgery, Leiden University Medical Centre, Leiden, The Netherlands.
  • Ten Dijke P; Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
EMBO J ; 42(10): e112806, 2023 05 15.
Article em En | MEDLINE | ID: mdl-36994542
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-ß 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-ß-induced EMT, migration, and extravasation in cancer cells. Unbiased pathway analysis demonstrated that LITATS1 knockdown potently and selectively potentiates TGF-ß/SMAD signaling. Mechanistically, LITATS1 enhances the polyubiquitination and proteasomal degradation of TGF-ß type I receptor (TßRI). LITATS1 interacts with TßRI 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-ß/SMAD signaling and EMT.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Carcinoma Pulmonar de Células não Pequenas / RNA Longo não Codificante / Neoplasias Pulmonares Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Carcinoma Pulmonar de Células não Pequenas / RNA Longo não Codificante / Neoplasias Pulmonares Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article