Beyond focal adhesions: integrin-linked kinase associates with tubulin and regulates mitotic spindle organization.
Integrin-linked kinase (ILK) is a member of a multiprotein complex at focal adhesions which interacts with actin. Here, it functions as a kinase and adapter protein to regulate diverse cellular processes. Gene knockout studies have demonstrated critical roles for ILK in embryonic development and in organ and tissue homeostasis. However, ILK is overexpressed in many human cancers and experimental overexpression in non-transformed cells results in the acquisition of several oncogenic phenotypes. Proteomic based approaches to identify ILK binding partners have now identified tubulins and many centrosomal and mitotic spindle associated proteins as ILK interactors in addition to the expected focal adhesion, actin interacting, proteins. Further analysis has shown that ILK co-localizes with several of these proteins to the centrosome and inhibition or depletion of ILK causes mitotic spindle defects by disrupting Aurora A kinase/TACC3/ch-TOG interactions. Here we discuss the finding that ILK is a member of a tubulin-based multiprotein complex at the centrosome, and identify potential mechanisms by which ILK regulates the organization of the mitotic spindle. We also discuss the implications of ILK's mitotic role for cancer progression and highlight the potential use of ILK inhibitors as novel anti-mitotic chemotherapeutics.
Fielding
Andrew B
AB
Department of Cancer Genetics, British Columbia Cancer Research Centre of BC Cancer Agency, Vancouver, British Columbia, Canada.
Dobreva
Iveta
I
Dedhar
Shoukat
S
D000199:Actins / Q000378:metabolism*; D000818:Animals; D064127:Aurora Kinases; D018385:Centrosome / Q000378:metabolism*; D004265:DNA Helicases / Q000378:metabolism; D022001:Focal Adhesions / Q000378:metabolism*; D006801:Humans; D016023:Integrins / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D040901:Proteomics; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D008941:Spindle Apparatus / Q000378:metabolism*; D014404:Tubulin / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism; D000099200:Scaffold Protein ILK
D000199:Actins; D064127:Aurora Kinases; D004265:DNA Helicases; D016023:Integrins; D008869:Microtubule-Associated Proteins; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D012097:Repressor Proteins; D014404:Tubulin; D051176:beta Catenin; D000099200:Scaffold Protein ILK; C454180:CKAP5 protein, human; C514503:GSKIP protein, human