Cell death & disease, 2023-02, Vol.14 (2), p.83-83, Article 83
2023
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- Autor(en) / Beteiligte
- Titel
- VHL-HIF-2α axis-induced SEMA6A upregulation stabilized β-catenin to drive clear cell renal cell carcinoma progression
- Ist Teil von
- Cell death & disease, 2023-02, Vol.14 (2), p.83-83, Article 83
- Ort / Verlag
- London: Nature Publishing Group UK
- Erscheinungsjahr
- 2023
- Quelle
- Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
- Beschreibungen/Notizen
- SEMA6A is a multifunctional transmembrane semaphorin protein that participates in various cellular processes, including axon guidance, cell migration, and cancer progression. However, the role of SEMA6A in clear cell renal cell carcinoma (ccRCC) is unclear. Based on high-throughput sequencing data, here we report that SEMA6A is a novel target gene of the VHL - HIF - 2α axis and overexpressed in ccRCC. Chromatin immunoprecipitation and reporter assays revealed that HIF-2α directly activated SEMA6A transcription in hypoxic ccRCC cells. Wnt /β-catenin pathway activation is correlated with the expression of SEMA6A in ccRCC; the latter physically interacted with SEC62 and promoted ccRCC progression through SEC62 -dependent β-catenin stabilization and activation. Depletion of SEMA6A impaired HIF-2α -induced Wnt /β-catenin pathway activation and led to defective ccRCC cell proliferation both in vitro and in vivo. SEMA6A overexpression promoted the malignant phenotypes of ccRCC, which was reversed by SEC62 depletion. Collectively, this study revealed a potential role for VHL - HIF-2α - SEMA6A - SEC62 axis in the activation of Wnt /β-catenin pathway. Thus, SEMA6A may act as a potential therapeutic target, especially in VHL -deficient ccRCC.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2041-4889eISSN: 2041-4889DOI: 10.1038/s41419-023-05588-4Titel-ID: cdi_doaj_primary_oai_doaj_org_article_8d78d7caf9aa47dfb63e8eeb1251aa85
- Format
- –
- Schlagworte
- 13/1, 13/21, 13/51, 692/699/67/1059, 692/699/67/2195, 82/1, Antibodies, Axon guidance, Basic Helix-Loop-Helix Transcription Factors - genetics, Basic Helix-Loop-Helix Transcription Factors - metabolism, beta Catenin - genetics, beta Catenin - metabolism, Biochemistry, Biomedical and Life Sciences, Carcinoma, Renal Cell - pathology, Cell activation, Cell Biology, Cell Culture, Cell Line, Tumor, Cell migration, Cell proliferation, Chromatin, Clear cell-type renal cell carcinoma, Gene Expression Regulation, Neoplastic, Humans, Hypoxia, Hypoxia-Inducible Factor 1, alpha Subunit - metabolism, Immunology, Immunoprecipitation, Kidney cancer, Kidney Neoplasms - metabolism, Kinases, Life Sciences, Next-generation sequencing, Phenotypes, Semaphorins - genetics, Semaphorins - metabolism, Therapeutic targets, Up-Regulation, VHL protein, Von Hippel-Lindau Tumor Suppressor Protein - genetics, Von Hippel-Lindau Tumor Suppressor Protein - metabolism, Wnt protein, β-Catenin