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EGR1 Mediates Riluzole-Induced Apoptosis in Osteosarcoma via the Yap/p73-Bax Signaling Axis.
Syeda Maryam Azeem1, Shraddha ChandThakuri2, Pooja Prakash Rao3
1Ph.D. Program in Biology, The Graduate Center of the City University of New York, New York, USA.
Biorxiv : the Preprint Server for Biology
|November 24, 2025
Summary
Riluzole, a potential osteosarcoma treatment, boosts apoptosis by increasing Early Growth Response 1 (EGR1) expression. EGR1 then works with Yap/p73 to activate Bax, promoting cancer cell death.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Osteosarcoma (OS) is the most common primary bone cancer in young adults (10-30 years).
- Current OS survival rates have stagnated despite therapeutic advancements.
- Riluzole, a glutamate receptor antagonist, shows promise by inducing apoptosis in OS cells.
Purpose of the Study:
- To investigate the role of Early Growth Response 1 (EGR1) in Riluzole-mediated apoptosis in osteosarcoma.
- To elucidate the molecular mechanism by which Riluzole induces apoptosis in OS.
Main Methods:
- Assessed Riluzole's effect on EGR1 expression in OS cell lines and patient-derived xenografts (PDX).
- Utilized chromatin immunoprecipitation followed by qPCR to confirm EGR1 binding to the Bax promoter.
- Performed immunohistochemistry on xenograft tumors to evaluate EGR1, cleaved caspase-3, and NUMA levels.
Main Results:
- Riluzole significantly upregulated EGR1 expression in all tested OS cell lines.
- Confirmed direct binding of EGR1, Yap/p73 to the Bax promoter, enhancing Bax expression.
- Observed increased EGR1 and cleaved caspase-3, with decreased NUMA in Riluzole-treated xenografts, indicating apoptosis and reduced proliferation.
Conclusions:
- Riluzole promotes osteosarcoma apoptosis via upregulation of EGR1.
- EGR1 cooperates with Yap/p73 to enhance Bax expression, a key apoptotic pathway.
- Riluzole represents a promising therapeutic strategy for OS by modulating the EGR1/Yap/p73/Bax signaling axis.
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