Integrin-Linked Kinase Regulates Cytoskeletal Dynamics and Cytokinesis in Retinoblastoma Cell Lines

During cell division integrin-linked kinase (ILK) has been shown to regulate microtubule dynamics and centrosome clustering, processes involved in cell cycle progression and malignant transformation.  In this study we examine the effects of a selective ILK inhibitor, QLT-0267 on mitotic function in human retinoblastoma cell lines.  These retinal cancer cells have elevated expression of ILK and are caused by the loss of function of two gene alleles (Rb1) that encode the retinoblastoma tumour suppressor, a principal controller of the cell cycle.  We show that exposure to QLT-0267 results in a concentration-dependent increase in nuclear area and an accumulation of multinucleated cells over time.  In these cells, aberrant cytokinesis and karyokinesis correlate with altered mitotic spindle organization and decreased levels of cortical F-actin.  Downregulation of ILK also decreases proliferation while increasing mitotic figures and apoptosis.  Additionally, forms of extreme, asymmetric cytokinesis are observed in QLT-0267 treated cultures whereby F-actin staining at the cleavage furrow no longer bifurcates nuclear material.  Future aims of this study are to continue unravelling ILK-related cytoskeletal changes underlying cytokinesis in retinoblastoma cells, and its ultimate effects on cancer progression.