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A non-catalytic function for RAD18 in sustaining glioblastoma proliferation
Nour Benbahouche1, Antoine Aze1, Aurore Siegfried2
1IGH, Univ Montpellier, CNRS, Montpellier, France.
Cell Reports
|July 3, 2026
Summary
RAD18 (E3) ubiquitin ligase promotes glioblastoma growth and stem cell renewal independently of DNA damage. Targeting RAD18 may sensitize brain tumors to therapy.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- RAD18 (E3) ubiquitin ligase is overexpressed in glioblastoma.
- RAD18 is a regulator of DNA damage tolerance and double-strand break repair.
Purpose of the Study:
- To investigate the role of RAD18 in glioblastoma proliferation and tumorigenesis.
- To elucidate the mechanism by which RAD18 promotes glioblastoma growth.
Main Methods:
- RAD18 downregulation and overexpression studies in glioblastoma cell lines.
- Cell cycle analysis and senescence assays.
- Studies in orthotropic xenograft mouse models.
- Investigation of RAD18 interaction with NF2 and YAP1.
Main Results:
- RAD18 promotes glioblastoma cell proliferation, stem cell self-renewal, and tumor growth, independent of its catalytic activity.
- RAD18 downregulation causes G1 cell cycle arrest and senescence without increasing DNA damage.
- RAD18 enhances non-transformed cell growth and oncogenic transformation.
- RAD18 interacts with and negatively regulates the NF2 tumor suppressor, stabilizing YAP1.
Conclusions:
- RAD18 is a key driver of glioblastoma progression.
- RAD18's oncogenic function involves the NF2/YAP1 pathway.
- RAD18 represents a potential therapeutic target for glioblastoma.
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