Related Experiment Video
Updated: May 24, 2026
04:01
Revealing the Ferroptotic Phenotype of Medulloblastoma
Published on: March 15, 2024
Stress granules restrain ferroptosis by sequestering ferritin
Zehe Ge1,2, Zihan Wang2, Erjie Zhao2
1Jiangsu Key Laboratory of Innovative Cancer Diagnosis and Therapeutics, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China.
Nature Cell Biology
|May 22, 2026
Summary
Disrupting stress granules (SGs) sensitizes glioblastoma stem cells (GSCs) to standard treatments by enabling ferroptosis. A small molecule targeting SG proteins restores treatment sensitivity in preclinical models.
Area of Science:
- Oncology
- Cell Biology
- Biochemistry
Background:
- Glioblastoma stem cells (GSCs) exhibit resistance to standard therapies like irradiation (IR) and temozolomide (TMZ).
- Stress granules (SGs), cellular aggregates formed under stress, are implicated in cancer cell survival and treatment resistance.
Purpose of the Study:
- To investigate the role of stress granules (SGs) in glioblastoma stem cell (GSC) resistance to IR/TMZ.
- To elucidate the mechanism by which SGs regulate ferroptosis in GSCs.
- To identify therapeutic strategies targeting the SG-ferroptosis axis.
Main Methods:
- Proteomic profiling of SG proteins in GSCs.
- Investigating the interaction between G3BP1 and ferritin light chain.
- Utilizing small molecule ciwujianoside C3 to disrupt G3BP1-ferritin interaction.
- In vitro and in vivo preclinical models of glioblastoma.
Main Results:
- Disruption of SGs sensitizes GSCs to IR/TMZ via ferroptosis induction.
- G3BP1 interacts with ferritin light chain in an oxidation-dependent manner, sequestering ferritin into SGs.
- This SG-mediated sequestration limits labile iron and prevents ferritinophagy, thereby inhibiting ferroptosis.
- Ciwujianoside C3 disrupts this interaction, mitigating SG-mediated ferroptosis restriction and resensitizing GSCs to IR/TMZ.
Conclusions:
- Stress granules negatively regulate ferroptosis in GSCs by sequestering iron-related proteins like ferritin.
- Targeting the SG-ferroptosis axis represents a promising therapeutic strategy for glioblastoma treatment.
- This approach may also be applicable to other cancer types exhibiting resistance to conventional therapies.
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