IQGAP Family Proteins in Colorectal Cancer: Molecular Mechanisms and Prognostic Implications

Colorectal cancer (CRC) remains a leading cause of cancer-related morbidity and mortality worldwide, and the molecular mechanisms driving its progression and metastasis remain incompletely understood. Increasing evidence highlights the role of IQ motif-containing GTPase-activating proteins (IQGAPs)—a family of scaffold proteins consisting of IQGAP1, IQGAP2, and IQGAP3—in regulating multiple signaling pathways involved in tumor development. This narrative review provides an overview of the molecular roles of IQGAP family proteins in CRC, focusing on their involvement in oncogenic signaling and their potential prognostic significance. Current evidence suggests that IQGAP family members play distinct and sometimes opposing roles in CRC biology. IQGAP1 is frequently overexpressed and acts as a scaffold that activates ERK/MAPK and β-catenin signaling, promoting proliferation, invasion, and metastasis. In contrast, IQGAP2 exhibits tumor-suppressive properties, with reduced expression associated with more aggressive disease and unfavorable outcomes. Meanwhile, IQGAP3 has emerged as a potential oncogenic driver, where its upregulation correlates with enhanced tumor growth, metastatic potential, and poorer survival, possibly through PI3K-related signaling. Together, these findings highlight the context-dependent roles of IQGAP proteins in CRC and suggest their potential as novel biomarkers and therapeutic targets. Further validations are needed to explore the clinical utility of IQGAP proteins in CRC.