title: Overexpression of the human ZNF300 gene enhances growth and metastasis of cancer cells through activating NF-kB pathway.
abstract: Zinc finger proteins (ZNF) play important roles in various physiological processes. Here we report that ZNF300, a novel zinc finger protein, identified specifically in humans, promotes tumour development by modulating the NF-κB pathway. Inflammatory factors were found to induce ZNF300 expression in HeLa cell line, and ZNF300 expression further enhanced NF-κB signalling by activating TRAF2 and physically interacting with IKKβ. Furthermore, ZNF300 overexpression increased ERK1/2 phosphorylation and the expression of c-myc, IL-6, and IL-8 but decreased the expression of p21(waf-1)  and p27(Kip1) ; whose down-regulation led to the opposite effect. Most importantly, ZNF300 overexpression stimulated cancer cell proliferation in vitro and significantly enhanced tumour development and metastasis in mouse xenograft model, while knocking down ZNF300 led to the opposite effects. We have identified a novel function for ZNF300 in tumour development that may uniquely link inflammation and NF-κB to tumourigenesis in humans but not in mice.
authors.affiliation: The State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: Xian-guo
authors.initials: XG
authors.lastname: Wang
authors.forename: Jun-hua
authors.initials: JH
authors.lastname: Xu
authors.forename: Xiang-Peng
authors.initials: XP
authors.lastname: Wu
authors.forename: Hong-ling
authors.initials: HL
authors.lastname: Qiu
authors.forename: Hong
authors.initials: H
authors.lastname: Yi
authors.forename: Wen-Xin
authors.initials: WX
authors.lastname: Li
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000473:pathology*; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D051550:I-kappa B Kinase / Q000737:chemistry / Q000378:metabolism; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D020935:MAP Kinase Signaling System; D051379:Mice; D008819:Mice, Nude; D016328:NF-kappa B / Q000378:metabolism*; D009362:Neoplasm Metastasis / Q000235:genetics* / Q000473:pathology*; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis; D012097:Repressor Proteins / Q000235:genetics*; D015398:Signal Transduction; D047992:TNF Receptor-Associated Factor 2 / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis; D023041:Xenograft Model Antitumor Assays
chemical_list: C508606:CXCL8 protein, human; D004268:DNA-Binding Proteins; C508600:IL6 protein, human; D015850:Interleukin-6; D016209:Interleukin-8; C489427:MYC protein, human; D016328:NF-kappa B; D016271:Proto-Oncogene Proteins c-myc; D012097:Repressor Proteins; C087628:TCEAL1 protein, human; D047992:TNF Receptor-Associated Factor 2; D014157:Transcription Factors; C485905:ZNF300 protein, human; D050760:Cyclin-Dependent Kinase Inhibitor p27; D051550:I-kappa B Kinase