We describe a novel CTRP8‐RXFP1‐Janus‐activated kinase 3‐STAT3 signaling cascade that enhances cellular protein content and activity of small Rho GTPase Cdc42, which directs F‐actin cytoskeletal remodeling, filopodia formation, and increased glioblastoma multiforme migration. Here, CDC42 is linked to glioblastoma.