PDGF‐D Promotes Epithelial–Mesenchymal Transition of Glioma Cells Through the NF‐κB/NOTCH1 Pathway

PMCID: PMC12175480

PMID: 40530904

DOI: 10.1002/cam4.71002

Journal: Cancer medicine

Publication Date: 2025-6-18

Authors: Li Y, Zhao Y, Shi M, Ma X, Jia M, et al.

Key Points

• PDGF-D expression positively correlates with glioma malignancy and WHO tumor grade
• Knockdown of PDGF-D significantly reduced colony formation by p < 0.0001 in LN18 cells
• PDGF-D represents a potential therapeutic target for inhibiting glioma progression and metastasis

Summary

This translational research investigated the role of platelet-derived growth factor-D (PDGF-D) in glioma progression, revealing a critical molecular mechanism underlying tumor malignancy. By analyzing the Chinese Glioma Genome Atlas and conducting comprehensive in vitro and in vivo experiments, researchers demonstrated that PDGF-D is significantly upregulated in high-grade gliomas and correlates with poor prognosis.

The study uncovered a novel molecular pathway where PDGF-D promotes epithelial-mesenchymal transition (EMT), migration, and invasion of glioma cells through the NF-κB/NOTCH1 signaling axis. Mechanistically, PDGF-D knockdown reduced phosphorylated p65 and NOTCH1 expression, inhibiting clonal proliferation and invasive potential. Conversely, PDGF-D overexpression activated these pathways, enhancing the malignant phenotype of glioma cells.