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The mitotic functions of integrin-linked kinase

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Abstract

The cytoskeleton is composed of three major constituents: actin filaments, intermediate filaments and microtubules. These are vital for numerous normal cellular processes including cell spreading and migration, intracellular organelle transport, mechanical strength, mitosis and cytokinesis. Deregulation of cytoskeletal components can lead to cells developing several oncogenic phenotypes; for example increased migration and invasiveness, defects in cellular morphogenesis and genetic instabilities due to errors in mitosis and cytokinesis. Integrin-linked kinase (ILK) is a protein with well established roles in regulating actin cytoskeletal reorganization, survival, proliferation, cell migration, invasion and epithelial to mesenchymal transition, and is therefore essential to normal cell physiology. In addition, ILK is overexpressed or deregulated in a number of human cancers and when experimentally overexpressed leads to the acquisition of a number of oncogenic phenotypes, some of which, such as increased cell migration, are actin-dependent. Here we shall focus on the recent finding that ILK also regulates the microtubule cytoskeleton and is involved in mitotic spindle organization. Therefore its deregulation may also lead to errors in cell division causing genomic instability, potentially further contributing to cancer development. In light of these findings, the therapeutic potential of the anti-mitotic effects of genetic or pharmacological inhibition of ILK will also be discussed.

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Acknowledgements

S.D. acknowledges grant support from the National Cancer Institute of Canada (NCIC) with funds raised through the Canadian Cancer Society (CCS) and the Terry Fox Foundation, and from the Canadian Institutes for Health Research (CIHR).

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  1. Department of Cancer Genetics, British Columbia Cancer Research Centre of the BC Cancer Agency, 675 West 10th Avenue, Vancouver, BC, Canada, V5Z1L3

    Andrew B. Fielding & Shoukat Dedhar

  2. Department of Biochemistry and Molecular Biology, Life Sciences Institute, University of British Columbia, Vancouver, BC, Canada

    Shoukat Dedhar

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  1. Andrew B. Fielding
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Correspondence to Shoukat Dedhar.

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Fielding, A.B., Dedhar, S. The mitotic functions of integrin-linked kinase. Cancer Metastasis Rev 28, 99–111 (2009). https://doi.org/10.1007/s10555-008-9177-0

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