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Related Experiment Video

Updated: Jan 18, 2026

Quantitative PCR-based Assay to Measure Sonic Hedgehog Signaling in Cellular Model of Ciliogenesis

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Published on: January 31, 2025

RAC1 Regulates Shh-Medulloblastoma Growth via GLI-Mediated Transcription.

Nitish Jangde, Mi Hye Lee, Luz Ruiz

Biorxiv : the Preprint Server for Biology

|June 6, 2025

Summary

We identified RAC1 as a key driver in Shh-medulloblastoma (MB) progression. Inhibiting RAC1 with the drug candidate GYS32661 reduced tumor growth and improved survival in preclinical models, offering a potential new therapy for MB.

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Isolation, Enrichment, and Maintenance of Medulloblastoma Stem Cells

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Published on: September 1, 2010

Area of Science:

Oncology
Molecular Biology
Genetics

Background:

Medulloblastoma (MB) is the most common malignant pediatric brain tumor.
Current therapies are insufficient for treating MB proliferation, migration, and metastasis.
The small GTPase RAC1 regulates actin dynamics, proliferation, and migration in various cancers but remains uncharacterized in MB.

Purpose of the Study:

To investigate the role of RAC1 in Shh-MB.
To identify RAC1 as a potential therapeutic target for MB.

Main Methods:

Assessed RAC1 levels in MB tissue.
Depleted RAC1 in Shh-MB cells to evaluate proliferation and migration.
Investigated RAC1's mechanism of action on Shh pathway transcription factors.
Tested the efficacy of the RAC1 inhibitor GYS32661 in an orthotopic Shh-MB mouse model.

Main Results:

RAC1 levels are elevated in MB tissue compared to normal cerebellum.
RAC1 depletion significantly reduced Shh-MB cell proliferation and migration in vitro.
RAC1 directly binds to the GLI1 promoter, regulating Shh pathway transcription.
The brain-penetrant RAC1 inhibitor GYS32661 reduced MB tumor growth and increased survival in mice.

Conclusions:

RAC1 is a critical regulator of Shh-MB progression.
Targeting RAC1 with GYS32661 shows therapeutic potential for both pediatric and adult MB.
RAC1 represents a novel, druggable target for Shh-dependent medulloblastoma.