Related Experiment Video
Updated: Jun 13, 2026
A Human Glioblastoma Organotypic Slice Culture Model for Study of Tumor Cell Migration and Patient-specific Effects of Anti-Invasive Drugs
Published on: July 20, 2017
Sonic Hedgehog/GLI₁ signaling pathway inhibition restricts cell migration and invasion in human gliomas
Ke Wang1, Li Pan, Xiaoming Che
1Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.
Abstract:
Recent studies have shown that aberrant activation of Sonic Hedgehog (SHH)/GLI1 signaling pathway is involved in many kinds of human malignancies. Both in vitro and in vivo experiments demonstrate that inhibiting the pathway results in tumor regression for a fraction of gliomas which harbor an active pathway. However, little is known about the linkage between the SHH/GLI1 signaling pathway and cell migration and invasion in gliomas. In this study, we showed that GLI1 expression closely correlates with pathological grades of human gliomas by immunohistochemistry analysis of 110 cases of surgically-resected glioma tissues. Moreover, we used cyclopamine and RNA interference technique to block the SHH/GLI1 signaling to investigate the in vitro changes of glioma cells. The result showed that suppression of the pathway markedly inhibited glioma cell migration and invasion. The following quantitative RT-PCR analysis showed that decreased expressions of Snail, MMP9, and increased E-cadherin expression coincided with GLI1 knockout. Collectively, our results raise the possibility that SHH/GLI1 is a potentially anti-invasive target for therapeutic intervention in human gliomas.
Insights
Aberrant Sonic Hedgehog (SHH)/GLI1 pathway activation drives glioma progression. Inhibiting this pathway significantly reduces glioma cell migration and invasion, suggesting it as a potential therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Aberrant activation of the Sonic Hedgehog (SHH)/GLI1 signaling pathway is implicated in various human cancers.
- While SHH/GLI1 pathway inhibition shows promise in treating some gliomas, its role in glioma cell migration and invasion remains unclear.
Purpose of the Study:
- To investigate the correlation between GLI1 expression and glioma pathological grades.
- To determine the effect of SHH/GLI1 pathway inhibition on glioma cell migration and invasion in vitro.
Main Methods:
- Immunohistochemistry analysis of 110 glioma tissues to assess GLI1 expression.
- In vitro experiments using cyclopamine and RNA interference to inhibit the SHH/GLI1 pathway.
- Quantitative RT-PCR to analyze gene expression changes.
Main Results:
- GLI1 expression positively correlated with glioma pathological grades.
- Inhibition of the SHH/GLI1 pathway significantly reduced glioma cell migration and invasion.
- Pathway suppression led to decreased Snail and MMP9 expression and increased E-cadherin expression.
Conclusions:
- The SHH/GLI1 signaling pathway is linked to glioma cell invasion and progression.
- Targeting the SHH/GLI1 pathway may offer a novel therapeutic strategy to combat glioma invasion.
Related Concept Videos
02:33Hedgehog Signaling Pathway
02:33Hedgehog Signaling Pathway
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...