The IQGAP family consists of evolutionarily conserved scaffold proteins, IQGAP1, IQGAP2, and IQGAP3. IQGAP1 is 62 and 59% identical at the level of amino acid sequence to IQGAP2 and IQGAP3, respectively. IQGAPs possess the same domain structure with the individual motifs being highly homologous among IQGAPs. The conservation is even higher between IQGAP1 and IQGAP2. While the WW domain is 30% identical, other four motifs are 70 to 93% identical between both IQGAPs. Despite the high level identity, IQGAP1 and IQGAP2 display opposite impact on tumorigenesis. IQGAP1 is the most thoroughly examined, and clearly promotes cancer formation via its scaffold functions in facilitating the Raf-Mek-Erk and Wnt signalling. On the other hand, IQGAP2 is much less investigated and suppresses tumorigenesis. We will review the evidence that supports IQGAP2 reducing tumorigenesis, discuss its tumour suppression in the context of our updated knowledge on IQGAP1, and outline some future directions. Our emphasis will be placed on prostate cancer.
