Inactivation of Tumor Suppressor CYLD Inhibits Fibroblast Reprogramming to Pluripotency.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37894364", "kind": "science-record", "revision": 3, "content_hash": "sha256:a163d22d993d733eb68cfc40ddb5bffc092449190cc5774658817d5560095137", "created_at": "2026-11-01T19:02:45Z", "updated_at": "2026-11-01T21:31:48Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Inactivation of Tumor Suppressor CYLD Inhibits Fibroblast Reprogramming to Pluripotency.", "doi": "10.3390/cancers15204997", "pmid": "37894364", "authors": ["Nikolaos Bekas", "Martina Samiotaki", "Maria Papathanasiou", "Panagiotis Mokos", "Athanasios Pseftogas", "Konstantinos Xanthopoulos", "Dimitris Thanos", "George Mosialos", "Dimitra Dafou"], "journal": "Cancers", "year": 2023, "abstract": "CYLD is a tumor suppressor gene coding for a deubiquitinating enzyme that has a critical regulatory function in a variety of signaling pathways and biological processes involved in cancer development and progression, many of which are also key modulators of somatic cell reprogramming. Nevertheless, the potential role of CYLD in this process has not been studied. With the dual aim of investigating the involvement of CYLD in reprogramming and developing a better understanding of the intricate regulatory system governing this process, we reprogrammed control (CYLDWT/WT) and CYLD DUB-deficient (CYLDΔ9/Δ9) mouse embryonic fibroblasts (MEFs) into induced pluripotent stem cells (iPSCs) through ectopic overexpression of the Yamanaka factors (Oct3/4, Sox2, Klf4, c-myc). CYLD DUB deficiency led to significantly reduced reprogramming efficiency and slower early reprogramming kinetics. The introduction of WT CYLD to CYLDΔ9/Δ9 MEFs rescued the phenotype. Nevertheless, CYLD DUB-deficient cells were capable of establishing induced pluripotent colonies with full spontaneous differentiation potential of the three germ layers. Whole proteome analysis (Data are available via ProteomeXchange with identifier PXD044220) revealed that the mesenchymal-to-epithelial transition (MET) during the early reprogramming stages was disrupted in CYLDΔ9/Δ9 MEFs. Interestingly, differentially enriched pathways revealed that the primary processes affected by CYLD DUB deficiency were associated with the organization of the extracellular matrix and several metabolic pathways. Our findings not only establish for the first time CYLD's significance as a regulatory component of early reprogramming but also highlight its role as an extracellular matrix regulator, which has profound implications in cancer research.", "claims": [{"id": "claim-method", "statement": "A two-tailed Student’s t-test was used to estimate the statistical significance between two groups.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37894364", "locator": "sections[17] \"2.15. 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