IFI35 regulates non-canonical NF-κB signaling to maintain glioblastoma stem cells and recruit tumor-associated macrophages
© 2024. The Author(s), under exclusive licence to ADMC Associazione Differenziamento e Morte Cellulare..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
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| Enthalten in: |
Cell death and differentiation - (2024) vom: 09. Apr. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Li, Daqi [VerfasserIn] |
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Date Revised 09.04.2024 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1038/s41418-024-01292-8 |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM370837800 |
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| 245 | 1 | 0 | |a IFI35 regulates non-canonical NF-κB signaling to maintain glioblastoma stem cells and recruit tumor-associated macrophages |
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| 520 | |a © 2024. The Author(s), under exclusive licence to ADMC Associazione Differenziamento e Morte Cellulare. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 700 | 1 | |a Wang, Xiefeng |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Kexin |e verfasserin |4 aut | |
| 700 | 1 | |a Shan, Danyang |e verfasserin |4 aut | |
| 700 | 1 | |a Cui, Gaoyuan |e verfasserin |4 aut | |
| 700 | 1 | |a Yuan, Wei |e verfasserin |4 aut | |
| 700 | 1 | |a Lin, Qiankun |e verfasserin |4 aut | |
| 700 | 1 | |a Gimple, Ryan C |e verfasserin |4 aut | |
| 700 | 1 | |a Dixit, Deobrat |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Chenfei |e verfasserin |4 aut | |
| 700 | 1 | |a Gu, Danling |e verfasserin |4 aut | |
| 700 | 1 | |a You, Hao |e verfasserin |4 aut | |
| 700 | 1 | |a Gao, Jiancheng |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Yangqing |e verfasserin |4 aut | |
| 700 | 1 | |a Kang, Tao |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Junlei |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Hang |e verfasserin |4 aut | |
| 700 | 1 | |a Song, Kefan |e verfasserin |4 aut | |
| 700 | 1 | |a Shi, Zhumei |e verfasserin |4 aut | |
| 700 | 1 | |a Fan, Xiao |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Qiulian |e verfasserin |4 aut | |
| 700 | 1 | |a Gao, Wei |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Zhe |e verfasserin |4 aut | |
| 700 | 1 | |a Man, Jianghong |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Qianghu |e verfasserin |4 aut | |
| 700 | 1 | |a Lin, Fan |e verfasserin |4 aut | |
| 700 | 1 | |a Tao, Weiwei |e verfasserin |4 aut | |
| 700 | 1 | |a Mack, Stephen C |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Yun |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Junxia |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Chaojun |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Nu |e verfasserin |4 aut | |
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| 700 | 1 | |a Zhang, Qian |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Xiuxing |e verfasserin |4 aut | |
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