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| Status |
Public on Sep 22, 2017 |
| Title |
Tumor suppression via inhibition of SWI/SNF complex-dependent NF-kappaB activation [HeLaS3 subset] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
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).
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| Overall design |
Kazuyoshi,Kobayashi
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| Web link |
https://0-www-nature-com.brum.beds.ac.uk/articles/s41598-017-11806-9
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| |
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| Contributor(s) |
Hiramatsu H, Nakamura S, Kobayashi K, Haraguchi T, Iba H |
| Citation(s) |
28924147 |
| Submission date |
Jan 18, 2017 |
| Last update date |
Feb 20, 2018 |
| Contact name |
Kazuyoshi Kobayashi |
| E-mail(s) |
jgdfd547@gmail.com
|
| Organization name |
Chiba University
|
| Department |
Medical Mycology Research Center (MMRC)
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| Street address |
1-8-1 Inohana, Chuo-ku
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| City |
Chiba |
| ZIP/Postal code |
260-8673 |
| Country |
Japan |
| |
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| Platforms (1) |
| GPL21185 |
Agilent-072363 SurePrint G3 Human GE v3 8x60K Microarray 039494 [Probe Name Version] |
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| Samples (4)
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| This SubSeries is part of SuperSeries: |
| GSE93770 |
Tumor suppression via inhibition of SWI/SNF complex-dependent NF-kappaB activation |
|
| Relations |
| BioProject |
PRJNA362338 |
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