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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Mar 27, 2024 |
| Title |
IFI35 regulates non-canonical NF-κB signaling to maintain glioblastoma stem cells and recruit tumor-associated macrophages |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Glioblastoma (GBM) is the most aggressive malignant primary brain tumor characterized by a highly heterogeneous and immunosuppressive tumor microenvironment (TME). The symbiotic interactions between glioblastoma stem cells (GSCs) and tumor-associated macrophages (TAM) in the TME are critical for tumor progression. Here, we identified that IFI35, a transcriptional regulatory factor, plays both cell-intrinsic and cell-extrinsic roles in maintaining GSCs and the immunosuppressive TME. IFI35 induced non-canonical NF-kB signaling through proteasomal processing of p105 to the DNA-binding transcription factor p50, which heterodimerizes with RELB (RELB/p50), and activated cell chemotaxis in a cell autonomous manner. Further, IFI35 induced recruitment and maintenance of M2-like TAMs in TME in a paracrine manner. Targeting IFI35 effectively suppressed in vivo tumor growth and prolonged survival of orthotopic xenograft-bearing mice. Collectively, these findings reveal the tumor-promoting functions of IFI35 and suggest that targeting IFI35 or its downstream effectors may provide effective approaches to improve GBM treatment.
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| Overall design |
Comparative gene expression profiling analysis of ATAC-seq data for 839 cell and its KO derivatives (sgIFI35).
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| Contributor(s) |
Li D, Wang X, Chen K, Shan D, Yuan W, Lin Q, Gimple RC, Dixit D, Lu C, Gu D, Hao Y, Gao J, Li Y, Kang T, Yang J, Yu H, Song K, Shi Z, Chen Y, Zhang J, Fan X, Wu Q, Zhao L, Gao W, Zhu Z, Man J, Wang Q, Lin F, Tao W, Mack SC, Li C, Zhang N, You Y, Qian X, Yang K, Rich JN, Zhang Q, Wang X |
| Citation(s) |
38594444 |
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| Submission date |
Sep 07, 2023 |
| Last update date |
Jun 16, 2024 |
| Contact name |
Daqi Li |
| E-mail(s) |
bioldq@gmail.com
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| Phone |
+8618941341900
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| Organization name |
Nanjing Medicial University
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| Street address |
Longmian Avenue No.101
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| City |
Nanjing |
| ZIP/Postal code |
210095 |
| Country |
China |
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| Platforms (1) |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA1013953 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE242570_RAW.tar |
44.9 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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