To review the role of GLI3 in cancer, focusing on its dual regulatory functions and potential as a biomarker and therapeutic target.
Approach:
Integration of Evidence: Current evidence on GLI3 isoform processing, regulatory mechanisms, and functional consequences of altered GLI3 signaling across various tumor types was integrated.
Key Findings:
GLI3 has both oncogenic and tumor-suppressive effects that are context-dependent.
The balance between GLI3A (activator) and GLI3R (repressor) is crucial for tumor behavior.
Dysregulated GLI3 signaling is linked to epithelial–mesenchymal transition, cancer stem cell maintenance, immune remodeling, and therapeutic resistance.
GLI3 expression and isoform patterns may serve as diagnostic, prognostic, and susceptibility biomarkers.
Emerging therapeutic strategies target GLI3 through indirect modulation, direct inhibition, or combination approaches.
Interpretation:
GLI3 is identified as a pivotal regulator of tumor biology with potential clinical utility in precision oncology.
Limitations:
Challenges include developing isoform-specific detection methods.
Clarification of non-canonical regulatory mechanisms is needed.
Improved translational validation is required.
Conclusion:
This review identifies GLI3 as a pivotal regulator of tumor biology and highlights its potential as a target for further research.
