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

Abstract

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.

The oncogenic role ofStreptococcus gallolyticus subsp.gallolyticusis linked to activation of multiple cancer-related signaling pathways

“…Staining with phalloidin revealed strong disorganization of the actin cytoskeleton. These SGG-induced cytoskeleton rearrangements may be due to changes in the integrin/ILK/actin cytoskeleton signaling pathways [44][45][46][47].…”

“…These SGG-induced cytoskeleton rearrangements may be due to changes in the integrin/ILK/actin cytoskeleton signaling pathways [44][45][46][47].…”

Combination Effects of Integrin-linked Kinase and Abelson Kinase Inhibition on Aberrant Mitosis and Cell Death in Glioblastoma Cells

“…ILK was originally identified as a serine/threonine kinase [47]. Since then, ILK has been shown in hundreds of publications to promote phosphorylation of proteins and kinases and highly purified recombinant ILK has been unequivocally demonstrated to have protein kinase activity [48,49]. Moreover, small molecule inhibitors have been identified that bind specifically to the putative kinase domain [49].…”

Computational Drug Repurposing Approach to Identify Novel Inhibitors of ILK Protein for Treatment of Esophageal Squamous Cell Carcinoma

“…However, a recent study showed that ILK is a pseudokinase [29]. Subsequently, numerous studies have revealed that ILK plays a key role in epithelial-mesenchymal transition (EMT), invasion, and angiogenesis, suggesting that it could be an attractive target for tumor therapy [30][31][32]. In fact, some studies have shown that ILK is not only upregulated in a variety of malignancies but is also associated with a poor patient prognosis.…”