Based on the current studies, and previous findings, as a signaling platform that integrates heterotrimeric G protein signaling, leading to adjustments in the actin cytoskeleton, PDZ-RhoGEF might serve as an effector to fine-tune dynamic adjustments of migrating cancer cells, depending on the signaling input and the small Rho GTPase being activated: RhoA, Cdc42, or RhoJ. This evidence concerns the gene RHOA and cancer.