Cylindromatosis Lysine 63 Deubiquitinase (CYLD) Regulates NF-kB Signaling Pathway and Modulates Fibroblast and Endothelial Cells Recruitment in Nasopharyngeal Carcinoma

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...

Full description

Saved in:
Bibliographic Details
Published inCancers Vol. 12; no. 7; p. 1924
Main Authors Deng, Mingdan, Dai, Wei, Yu, Valen Zhuoyou, Tao, Lihua, Lung, Maria Li
Format Journal Article
LanguageEnglish
Published Basel MDPI AG 16.07.2020
MDPI
Subjects
Angiogenesis
Binding sites
Cell adhesion & migration
Cell cycle
Cell growth
Cell migration
Cell proliferation
Endothelial cells
Genes
Infiltration
Liver
Lysine
Metastases
Metastasis
Mutation
Nasopharyngeal carcinoma
Nasopharynx
NF-κB protein
Proteins
Ribonucleic acid
RNA
Signal transduction
Tumorigenesis
Tumorigenicity
Tumors
Online AccessGet full text

Cover

More Information
Summary: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.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers12071924