IQGAP3 is a GTPase-activating protein that functions as a critical oncogenic scaffold regulating cytoskeletal dynamics and cell signaling in cancer progression. Mechanistically, IQGAP3 activates multiple signaling pathways including RAS-ERK, TGF-β, PI3K/AKT, and Cdc42 cascades 1234. IQGAP3 is ubiquitously overexpressed across diverse human cancers—hepatocellular carcinoma, colorectal cancer, pancreatic cancer, gastric cancer, and glioma—where elevated expression correlates with aggressive clinicopathological features and poor prognosis 5623. In HCC, IQGAP3 overexpression promotes microvascular invasion by inducing hepatic stellate cell activation and detachment from endothelium while sustaining Rac1 activity to enhance trans-endothelial migration 5. IQGAP3 also drives epithelial-mesenchymal transition through TGF-β pathway activation and maintains intratumoral functional heterogeneity essential for tumor microenvironment formation 21. Clinically, IQGAP3 serves as a diagnostic and prognostic biomarker with high diagnostic accuracy (AUROC >0.95) in colorectal cancer 6, and IQGAP3-targeting therapeutic approaches show promise in reducing metastasis 5.