Integrin-linked kinase (ILK) is a ubiquitously expressed serine/threonine protein kinase involved in focal adhesion formation and regulates many cellular processes, such as cell adhesion, proliferation, migration, invasion, embryonic development and tissue homeostasis. Interestingly, aberrantly elevated ILK activity is also associated with a variety of human cancers. ILK is also known to be implicated in signalling pathways, such as WNT/b-catenin, MAPK and PI3K, which are often dysregulated in many cancers, including colorectal cancer (CRC). We identified and reported a novel role for ILK as a key mediator of innate immune Toll-like receptor (TLR) signalling via non-classical pathway activation of NF-kB (Ahmed et al., JBC 289:27776), a major pro-inflammatory transcription factor that plays an essential role in promoting CRC. Since ILK knockout mice are not viable and immune cells play critical roles in CRC, we generated mice with a selective deletion of the Ilk gene in myeloid cells (IlkloxP/loxP;LysMCre). Using a mouse model of colitis, we have recently shown that the myeloid-ILK deficiency ameliorated the pathology of disease along with reduced neutrophil infiltration, impaired inflammation response and elevated epithelial regeneration (Ahmed et al., J Immunol 199:2128). Moreover, myeloid-ILK-dependent inflammatory signalling in the mucosal epithelium was also therapeutically targeted using a global inhibitor of ILK during experimental colitis (Ahmed et al., J Immunol 199:2128). Since patients with inflammatory bowel diseases are at increased risk for colon cancer, we have investigated the effect of myeloid-ILK in mouse models of colitis-associated and APCmin/+-driven colon carcinogenesis. We aim to provide an insight into tumour biology by investigating the role of ILK in tumour-associated macrophage (TAM)-mediated tumour progression. Our data suggest a role for ILK in macrophage M2 polarization. Our observations also show that myeloid cell specific ILK deficient mice have a significant reduction in tumour burden compared with the control mice. Overall, our findings implicate ILK as a potential target for therapeutic intervention in both inflammatory diseases and cancers.