Journal article
IFI35 regulates non-canonical NF-κB signaling to maintain glioblastoma stem cells and recruit tumor-associated macrophages
Cell death and differentiation, Vol.31(6), pp.738-752
06/01/2024
DOI: 10.1038/s41418-024-01292-8
PMCID: PMC11165006
PMID: 38594444
Abstract
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.
Details
- Title: Subtitle
- IFI35 regulates non-canonical NF-κB signaling to maintain glioblastoma stem cells and recruit tumor-associated macrophages
- Creators
- Daqi Li - Nanjing Medical UniversityXiefeng Wang - Nanjing Medical UniversityKexin Chen - Nanjing Medical UniversityDanyang Shan - Nanjing Medical UniversityGaoyuan Cui - Nanjing Medical UniversityWei Yuan - Yancheng First People's HospitalQiankun Lin - Nanjing Medical UniversityRyan C. Gimple - Cleveland ClinicDeobrat Dixit - UPMC Hillman Cancer CenterChenfei Lu - Nanjing Medical UniversityDanling Gu - Nanjing Medical UniversityHao You - Nanjing Medical UniversityJiancheng Gao - Nanjing Medical UniversityYangqing Li - Model Animal Research CenterTao Kang - Nanjing Medical UniversityJunlei Yang - Nanjing Medical UniversityHang Yu - Nanjing Medical UniversityKefan Song - Nanjing Medical UniversityZhumei Shi - Nanjing Medical UniversityXiao Fan - Nanjing Medical UniversityQiulian Wu - University of Pittsburgh Medical CenterWei Gao - Nanjing Medical UniversityZhe Zhu - Columbia University Irving Medical CenterJianghong Man - National Center of Biomedical AnalysisQianghu Wang - Nanjing Medical UniversityFan Lin - Nanjing Medical UniversityWeiwei Tao - Huazhong Agricultural UniversityStephen C. Mack - St. Jude Children's Research HospitalYun Chen - Nanjing Medical UniversityJunxia Zhang - Nanjing Medical UniversityChaojun Li - Nanjing UniversityNu Zhang - Sun Yat-sen UniversityYongping You - Jiangsu Province HospitalXu Qian - Nanjing Medical UniversityKailin Yang - Cleveland ClinicJeremy N. Rich - University of Pittsburgh Medical CenterQian Zhang - Nanjing Medical UniversityXiuxing Wang - Nanjing Medical University
- Resource Type
- Journal article
- Publication Details
- Cell death and differentiation, Vol.31(6), pp.738-752
- DOI
- 10.1038/s41418-024-01292-8
- PMID
- 38594444
- PMCID
- PMC11165006
- NLM abbreviation
- Cell Death Differ
- ISSN
- 1350-9047
- eISSN
- 1476-5403
- Publisher
- Springer Nature
- Number of pages
- 15
- Grant note
- National Natural Science Foundation of China (National Science Foundation of China); National Natural Science Foundation of China (NSFC)
- Language
- English
- Date published
- 06/01/2024
- Academic Unit
- Radiation Oncology
- Record Identifier
- 9984696568202771
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