Related Experiment Video
Updated: Jan 8, 2026
Generation of CAR T Cells for Adoptive Therapy in the Context of Glioblastoma Standard of Care
Published on: February 16, 2015
Necroptotic signaling orchestrates glioblastoma malignancy and potentiates temozolomide response
Yuanyuan Li1, Yuxin Qiu1, Wenqing Gao1
1Shanghai Pudong Hospital and School of Life Sciences, State Key Laboratory of Genetics and Development of Complex Phenotypes, Shanghai Engineering Research Center of Industrial Microorganisms, Fudan University, Shanghai, China.
Abstract:
Glioblastoma (GBM), a highly aggressive form of glioma, poses serious harm to patients due to its extremely poor prognosis and severe resistance to chemotherapeutic agents. Although programmed necrosis (necroptosis) has been implicated in GBM progression, its precise function and biological significance in GBM remain incompletely defined. Here, we show that elevated expression of key necroptotic machinery proteins, including RIPK1 and MLKL, is positively associated with disease progression and predicts poor prognosis in glioma patients. Functionally, RIPK1 promotes glioblastoma cell proliferation, migration, and invasion. Genetic ablation of RIPK1 induces cell-cycle arrest and suppresses tumor growth in subcutaneous xenograft models, whereas pharmacological inhibition of RIPK1 with necrostatin-1 fails to restrict GBM cell expansion, suggesting that RIPK1 exerts oncogenic effects independent of its canonical necroptotic role. Notably, dual apoptosis- and necroptosis-inducing agents, ZZW115 and citronellol, synergize with temozolomide (TMZ)-the first-line chemotherapy for GBM-to enhance glioma cell death and increase tumor clearance in an orthotopic mouse glioma model. Collectively, these findings identify RIPK1 as a critical driver of glioma malignancy and underscore the therapeutic potential of activating necroptosis to augment TMZ efficacy, providing a framework for novel prognostic and treatment strategies in glioma.
Insights
Elevated RIPK1 protein drives glioblastoma growth and predicts poor prognosis. Activating programmed necrosis (necroptosis) enhances chemotherapy, offering new glioma treatment strategies.
Area of Science:
- Oncology
- Molecular Biology
- Cell Death Pathways
Background:
- Glioblastoma (GBM) is an aggressive brain tumor with poor prognosis and chemotherapy resistance.
- Programmed necrosis (necroptosis) is implicated in GBM, but its role is not fully understood.
Purpose of the Study:
- To investigate the role of necroptosis machinery proteins in glioma progression.
- To evaluate RIPK1's function in GBM and its potential as a therapeutic target.
- To explore novel therapeutic strategies combining necroptosis inducers with chemotherapy.
Main Methods:
- Analysis of RIPK1 and MLKL expression in glioma patient samples.
- In vitro studies using genetic ablation and pharmacological inhibition of RIPK1.
- In vivo studies using subcutaneous xenograft and orthotopic mouse glioma models.
- Assessment of combined treatment effects with necroptosis inducers and temozolomide (TMZ).
Main Results:
- Higher RIPK1 and MLKL expression correlates with GBM progression and poor prognosis.
- RIPK1 promotes GBM cell proliferation, migration, and invasion, independent of its necroptotic function.
- Genetic RIPK1 ablation suppresses tumor growth, but necrostatin-1 is ineffective.
- Dual apoptosis- and necroptosis-inducing agents synergize with TMZ to improve glioma cell death and tumor clearance in vivo.
Conclusions:
- RIPK1 is a key driver of glioma malignancy.
- Activating necroptosis can enhance the efficacy of temozolomide for GBM treatment.
- These findings provide a basis for new prognostic markers and therapeutic approaches for glioma.
More Related Videos
Related Concept Videos
03:03mTOR Signaling and Cancer Progression
The mTOR pathway or the...
01:19Interactions Between Signaling Pathways
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...