Emerging Roles of Regulator of G-protein Signaling 19 (RGS19) in Cancer Biology and Therapy
Maria Al Ibrahim, Saeed Al Mahri, Faisal Daham AlSahli, Iman Bhat, Shuja Shafi Malik, Sameer MohammadIntroduction:
G-protein-coupled Receptors (GPCRs) constitute the largest family of membrane receptors in humans and play central roles in transducing extracellular cues into tightly regulated intracellular responses. Precise control of GPCR signaling is essential for cellular homeostasis, as dysregulated signaling contributes to malignant transformation and cancer progression.
Method:
Aberrant GPCR activation promotes proliferation, survival, migration, invasion, angiogenesis, and immune evasion through engagement of multiple oncogenic pathways. The Regulators of Gprotein Signaling (RGS) proteins provide a critical regulatory layer within these pathways. They function as GTPase-activating proteins for Gα subunits, thereby shaping the magnitude, duration, and spatial organization of GPCR signals.
Results:
Increasing evidence indicates that RGS proteins exert context-dependent roles in cancer, acting either as tumor suppressors or as facilitators of oncogenic signaling depending on tissue type and molecular environment. RGS19, also known as GAIP, is a member of this family best known for its regulation of Gα_i/o-mediated signaling and involvement in receptor desensitization, signal compartmentalization, and inflammatory and metabolic processes. However, its contribution to tumor initiation, progression, and therapeutic response remains poorly defined.
Discussion:
Emerging studies suggest that RGS19 expression is altered in specific malignancies and may influence key cancer-associated signaling networks. In this review, we provide a comprehensive and critical synthesis of current knowledge on RGS19 in cancer. We examine its molecular and structural features, roles in GPCR-dependent and independent pathways, and functional impact on tumor biology, the tumor microenvironment, and treatment response.
Conclusion:
Finally, we highlight unresolved questions and outline future research directions to clarify the translational and therapeutic potential of targeting RGS19 in oncology.