NOTCH3 drives fatty acid oxidation and ferroptosis resistance in aggressive meningiomas.

ABSTRACT:

Purpose

NOTCH3 is increasingly implicated for its oncogenic role in many malignancies, including meningiomas. While prior work has linked NOTCH3 expression to higher-grade meningiomas and treatment resistance, the metabolic phenotype of NOTCH3 activation remains unexplored in meningioma.

Methods

We performed single-cell RNA sequencing on NOTCH3 + human meningioma cell lines. Using the CH157-MN meningioma cell model, we overexpressed NOTCH3 intracellular domain (ICD) and performed untargeted metabolomic, lipidomic, and bulk RNA sequencing analyses as well as functional metabolic assays.

Results

We show that NOTCH3 mediates a metabolic shift towards fatty acid oxidation (FAO), depleting lipid availability and conferring resistance to ferroptosis. Single-cell RNA sequenc

SUBMITTER: Sadagopan NS 

PROVIDER: S-EPMC12511256 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature