{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T04:30:31Z","timestamp":1784694631633,"version":"3.55.0"},"reference-count":64,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2020,7,16]],"date-time":"2020-07-16T00:00:00Z","timestamp":1594857600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002920","name":"Research Grants Council, University Grants Committee","doi-asserted-by":"publisher","award":["AoE\/M-06\/08"],"award-info":[{"award-number":["AoE\/M-06\/08"]}],"id":[{"id":"10.13039\/501100002920","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Nasopharyngeal carcinoma (NPC) is a malignant epithelial carcinoma of the nasopharynx. Cylindromatosis lysine 63 deubiquitinase (CYLD), a NF-kB inhibitor, was reported as one of the top mutated candidate genes in NPC. NF-kB is an inducible transcription factor, contributing to cancer via regulating inflammation, angiogenesis, cell proliferation, and metastasis. In this study, the impact of CYLD on regulating the NF-kB signaling pathway and its contribution to NPC development was studied using in vitro and in vivo functional assays, together with single cell RNA sequencing to understand the NPC tumor microenvironment. CYLD was downregulated in NPC clinical specimens and multiple cell lines. Functional assays revealed CYLD inhibits NPC cell proliferation and migration in vitro and suppresses NPC tumorigenicity and metastasis in vivo by negatively regulating the NF-kB signaling pathway. Additionally, CYLD was able to inhibit fibroblast and endothelial stromal cell infiltration into the NPC tumor microenvironment. These findings suggest that CYLD inhibits NPC development and provides strong evidence supporting a role for CYLD inhibiting fibroblast and endothelial stromal cell infiltration into NPC via suppressing the NF-kB pathway.<\/jats:p>","DOI":"10.3390\/cancers12071924","type":"journal-article","created":{"date-parts":[[2020,7,21]],"date-time":"2020-07-21T06:38:55Z","timestamp":1595313535000},"page":"1924","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Cylindromatosis Lysine 63 Deubiquitinase (CYLD) Regulates NF-kB Signaling Pathway and Modulates Fibroblast and Endothelial Cells Recruitment in Nasopharyngeal Carcinoma"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1502-9474","authenticated-orcid":false,"given":"Mingdan","family":"Deng","sequence":"first","affiliation":[{"name":"Department of Clinical Oncology, University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong (SAR), China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology, University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong (SAR), China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valen Zhuoyou","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology, University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong (SAR), China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lihua","family":"Tao","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology, University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong (SAR), China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2559-3626","authenticated-orcid":false,"given":"Maria Li","family":"Lung","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology, University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong (SAR), China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Lin, J.-H., Jiang, C.-Q., Ho, S.Y., Zhang, W.S., Mai, Z.-M., Xu, L., Lo, C.-M., and Lam, T.H. 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