New Perspectives on the Role of Integrin-Linked Kinase (ILK) Signaling in Cancer Metastasis

Cancer metastasis is a major barrier to the long-term survival of cancer patients. In cancer cells, integrin engagement downstream of cell-extracellular matrix (ECM) interactions results in the recruitment of cytoskeletal and signaling molecules to form multi-protein complexes to promote processes critical for metastasis. One of the major functional components of these complexes is Integrin Linked Kinase (ILK). Here, we discuss recent advances in our understanding of the importance of ILK as a signaling effector in processes linked to tumor progression and metastasis. New mechanistic insights as to the role of ILK in cellular plasticity, epithelial mesenchymal transition (EMT), migration, and invasion, including the impact of ILK on the formation of invadopodia, filopodia-like protrusions (FLPs), and Neutrophil Extracellular Trap (NET)-induced motility are highlighted. Recent findings detailing the contribution of ILK to therapeutic resistance and the importance of ILK as a potentially therapeutically tractable vulnerability in both solid tumors and hematologic malignancies are discussed. Indeed, pharmacologic inhibition of ILK activity using specific small molecule inhibitors is effective in curtailing the contribution of ILK to these processes, potentially offering a novel therapeutic avenue for inhibiting critical steps in the metastatic cascade leading to reduced drug resistance and increased therapeutic efficacy.