Periostin-mediated activation of NF-κB signaling promotes tumor progression and chemoresistance in glioblastoma

Periostin-mediated activation of NF-κB signaling promotes tumor progression and chemoresistance in glioblastoma

Abstract Glioblastoma (GBM) is the most aggressive form of diffuse glioma, characterized by high lethality. Temozolomide (TMZ)-based chemotherapy is a standard treatment for GBM, but development of chemoresistance poses a significant therapeutic challenge. Despite advances in understanding GBM biolo...

Full description

Saved in:
Bibliographic Details
Main Authors: Yu Shang, Yuxia Liang, Beichen Zhang, Wei Wu, Yihao Peng, Jin Wang, Ming Zhang, Chen Niu
Format: Article
Language:English
Published: Nature Portfolio 2025-04-01
Series:Scientific Reports
Subjects:
EMT-related phenotypes
NF-κB signaling
TMZ resistance
POSTN
Glioblastoma
Online Access:https://doi.org/10.1038/s41598-025-92969-8
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Abstract Glioblastoma (GBM) is the most aggressive form of diffuse glioma, characterized by high lethality. Temozolomide (TMZ)-based chemotherapy is a standard treatment for GBM, but development of chemoresistance poses a significant therapeutic challenge. Despite advances in understanding GBM biology, the mechanisms driving TMZ resistance remain unclear. Identifying vital molecular players involved in this resistance is crucial for developing new therapies. Our results indicated that periostin (POSTN) was significantly upregulated in GBM cell lines and patient samples, correlating with poorer clinical outcomes. POSTN overexpression enhanced GBM cell proliferation, migration, invasion, and chemoresistance, while lentiviral suppression of POSTN significantly reduced these behaviors. In vivo, bioluminescence imaging further confirmed the enhanced tumor growth associated with POSTN overexpression. Bioinformatics analysis was performed to explore the underlying molecular mechanism. The results revealed a strong correlation between POSTN and epithelial-mesenchymal transition (EMT) process and the tumor necrosis factor α (TNFα)-NF-κB signaling pathway. Moreover, exogenous POSTN silencing reduced IκB-kinase α (IKKα) phosphorylation, thereby decreasing NF-κB expression by limiting IκBα degradation. Collectively, our study demonstrated that POSTN-induced activation of NF-κB signaling and EMT processes promoted the malignancy and chemoresistance of GBM, suggesting that POSTN may serve as a reliable prognostic biomarker and potential therapeutic target for GBM.
ISSN:2045-2322

Similar Items