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Tumor suppression via inhibition of SWI/SNF complex-dependent NF-kappaB activation

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE93770 | GEO | 2017/09/22

SECONDARY ACCESSION(S): PRJNA362335

REPOSITORIES: GEO

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Tumor suppression via inhibition of SWI/SNF complex-dependent NF-?B activation.

Project description: Not available

| S-EPMC5603518 | biostudies-literature

Tumor suppression via inhibition of SWI/SNF complex-dependent NF-kappaB activation [HeLaS3 subset]

Project description:The transcription factor NF-kappaB is constitutively activated in many epithelial tumors but few NF-kappaB inhibitors are suitable for cancer therapy because of the broad biological effects of NF-κB. We previously reported that the d4 family (DPF1, DPF2, DPF3a/b) function as adaptor proteins linking NF-kappaB with the SWI/SNF complex. Here, we demonstrate that in epithelial tumor cell lines, exogenous expression of the highly conserved N-terminal 84-amino acid region of either DPF2 or DPF3a/b (designated “CT1”) has stronger inhibitory effects on anchorage-independent growth than single knockdown of any d4 protein, indicating that CT1 can function as an efficient dominant-negative mutant of the entire d4 family. By proximity ligation assays, CT1 was further shown to retain full function as an adaptor. Microarray analysis categorized NF-kappaB target genes by their CT1 sensitivity. Among CT1-sensitive genes, IL-6 was shown to strongly contribute to the anchorage-independent growth. Finally, exogenous CT1 expression efficiently suppressed tumor formation in a mouse xenograft model, suggesting that the d4 protein family could be a promising cancer therapy target. TNF-alpha induced gene expression in HeLaS3 cells was measured at 0 and 1 hour after the treatment of TNF-alpha (10 ng/ml). Beforehand, the cells were transduced with either lentivirus vector expressing a dominant-negative mutant of d4-family protein (named CT1) or with empty vector (control).

2017-09-22 | GSE93769 | GEO

Tumor suppression via inhibition of SWI/SNF complex-dependent NF-kappaB activation [A549 subset]

2017-09-22 | GSE93768 | GEO