IQGAPs in cancer. IQGAPs have been associated with neoplasia in various studies. In fact IQGAP1 mRNA levels are upregulated in various malignancies including colorectal, head and neck, breast, lung and liver cancers (White et al., 2009). This may come as no surprise given the implication of IQGAP1 with cell migration, invasion and adhesion as well as its scaffolding activity for the MAPK cascade, a pathway heavily associated with tumourigenesis (Xxxxxx et al., 2015; Xxxxx et al., 2009). In fact, after IQGAP1 was identified as a key regulator of H-Ras targeted tumourigenesis, it was suggested that the WW peptide of IQGAP1 could be therapeutically significant. This was supported by the fact that when it was systemically administered in a mouse model of pancreatic cancer, the WW peptide inhibited tumour growth and significantly increased survival rates (Xxxxxxx et al., 2013). Additionally, high levels of both IQGAP1 and IQGAP3 are required to drive squamous cell carcinoma in an in vivo xenograft skin model while the expression of the IQ domain in Ras driven organotypic tissues are substantially less proliferative disordered and invasive and display reduced p-ERK staining (Monteleon et al., 2015). Interestingly, in this study the WW domain did not exhibit any anti-tumourigenic effects (Monteleon et al., 2015). IQGAP1 is also important in invadopodia mediated matrix degradation by targeting MT1-MMP at the tip of the protrusions in MDA-MB-231 cells (Sakurai-Xxxxxx et al., 2008). While IQGAP2 is mainly expressed in the liver, IQGAP2 deficient mice develop hepatocellular carcinoma which is also accompanied by overexpression of IQGAP1 and loss of membrane E- cadherin (Xxxxxxx et al., 2008). In fact, mice deficient for both IQGAP1 and IQGAP2 had a decreased incidence of hepatocellular carcinoma and improved survival suggesting that the malignant phenotype resulting from loss of IQGAP2 is dependent on IQGAP1 (Xxxxxxx et al., 2008). These results together with the fact that decreased IQGAP2 expression is marked in gastric and prostate cancers support the notion of IQGAP2 being a tumour suppressor in spite of the tumorigenic activity of IQGAP1 (Xxxxx et al., 2015). IQGAP3 has also become increasingly associated with malignancy. IQGAP3 mRNA levels have been found to be upregulated in lung tumours where it is believed to drive tumourigenesis by interacting with ERK1 and promoting proliferation migration and invasion in A-549 lung cancer cells (Xxxx et al., 2014). Additionally, IQGAP3 expr...
