FABP4 facilitates epithelial-mesenchymal transition via elevating CD36 expression in glioma cells

Area of Science:

• Oncology
• Molecular Biology
• Cancer Research

Background:

• Glioblastoma multiforme (GBM) is an aggressive brain tumor with limited treatment options.
• Tumor cell epithelial-mesenchymal transition (EMT) is crucial for glioma progression and recurrence.
• Identifying key mediators of GBM EMT is essential for developing effective therapies.

Purpose of the Study:

• To investigate the role of Fatty acid-binding protein 4 (FABP4) in glioblastoma invasion and EMT.
• To elucidate the molecular mechanisms underlying FABP4-mediated glioma progression.
• To explore FABP4 as a potential therapeutic target for GBM.

Main Methods:

• Analysis of FABP4 expression in human GBM samples and correlation with glioma subtypes.
• In vitro gain-of-function and loss-of-function experiments to assess FABP4's impact on glioma cell invasiveness.
• Bioinformatic analysis (TCGA dataset) to identify FABP4-associated molecular signatures and pathways.
• In vitro mechanistic studies investigating FABP4-CD36-TGFβ signaling.
• In vivo assessment using an intracranial glioma model.

Main Results:

• FABP4 expression is elevated in GBM and associated with the mesenchymal subtype.
• FABP4 enhances glioma cell filopodia formation and invasiveness.
• FABP4 promotes an EMT-related molecular signature via CD36 and non-canonical TGFβ pathways.
• FABP4 inhibition reduces tumor progression in vivo.

Conclusions:

• FABP4 plays a critical role in regulating GBM invasion and EMT.
• FABP4-induced CD36 expression promotes EMT through non-canonical TGFβ signaling.
• Targeting FABP4 represents a promising therapeutic strategy for glioblastoma.