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Updated: Apr 14, 2026
Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics
Published on: March 15, 2024
LAPTM5-dependent lipophagy enhances ferroptosis sensitivity in glioma cells
Yan Zhang1, Lu Lu1, Qiuyu Zhao1
1Department of Pathology, The First Affiliated Hospital of Guilin Medical University, Guilin, China.
Background:
Lysosomal-associated protein transmembrane 5 (LAPTM5) is a transmembrane protein predominantly localized to late endosomes and lysosomes, with preferential expression in hematopoietic cells. Ferroptosis is an iron-dependent, non-apoptotic form of programmed cell death (PCD) that is driven by the lethal accumulation of lipid peroxides. Many studies have shown that ferroptosis is dependent on autophagy. Lipophagy is a selective form of autophagy by degrading lipid droplets (LDs) within autophagic vesicles to regulate lipid balance. Lipophagy can promote RAS-selective lethal 3 (RSL3)-induced ferroptosis. However, whether LAPTM5 regulates lipophagy to sensitize glioma cells to ferroptosis remains to be explored. Therefore, the objective of our study was to evaluate the potential role of LAPTM5 in ferroptosis.
Methods:
The expression profile of LAPTM5 in human glioma tissues was analyzed by using The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases, and immunohistochemistry. Glioma cells were treated with ferroptosis inducer erastin, and then the cell viability, glutathione (GSH), and malondialdehyde (MDA) were detected. Lipophagy was tested by laser confocal microscopy and proteins expression were detected by western blot.
Results:
Elevated expression of LAPTM5 was observed in glioma tissues compared to normal brain tissues, and its high expression level was associated with poorer patient prognosis. LAPTM5 promoted lipophagy in glioma cells. LAPTM5 enhanced the sensitivity of glioma cells to ferroptosis inducer erastin, while suppression of lipophagy inhibited LAPTM5-mediated sensitization to erastin.
Conclusions:
The finding that glioma cells with high LAPTM5 expression were more sensitive to ferroptosis inducers suggests that glioma patients with high LAPTM5 expression may be more responsive to ferroptosis-inducing therapies.
Insights
Lysosomal-associated protein transmembrane 5 (LAPTM5) promotes lipophagy, enhancing glioma cell sensitivity to ferroptosis. High LAPTM5 expression may predict better response to ferroptosis-inducing therapies in glioma patients.
Area of Science:
- Oncology
- Cell Death Mechanisms
- Molecular Biology
Background:
- Lysosomal-associated protein transmembrane 5 (LAPTM5) is a transmembrane protein found in late endosomes/lysosomes, primarily in hematopoietic cells.
- Ferroptosis, an iron-dependent programmed cell death, is linked to lipid peroxide accumulation and relies on autophagy.
- Lipophagy, a specific autophagy process, degrades lipid droplets and can promote ferroptosis.
Purpose of the Study:
- To investigate the role of LAPTM5 in regulating lipophagy and sensitizing glioma cells to ferroptosis.
- To determine if LAPTM5 expression correlates with glioma patient prognosis.
Main Methods:
- Analyzed LAPTM5 expression in human glioma tissues using TCGA, CGGA databases, and immunohistochemistry.
- Treated glioma cells with erastin (a ferroptosis inducer) and assessed cell viability, glutathione (GSH), and malondialdehyde (MDA) levels.
- Evaluated lipophagy via laser confocal microscopy and western blot analysis of protein expression.
Main Results:
- LAPTM5 expression was elevated in glioma tissues, correlating with poorer patient prognosis.
- LAPTM5 was found to promote lipophagy in glioma cells.
- LAPTM5 increased glioma cell sensitivity to erastin, an effect diminished by lipophagy suppression.
Conclusions:
- Elevated LAPTM5 expression in glioma correlates with increased sensitivity to ferroptosis inducers.
- Glioma patients with high LAPTM5 expression may benefit from ferroptosis-inducing therapies.
