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LIM Kinase and Cancer Metastasis

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Cytoskeleton and Human Disease

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Abstract

The members of the LIM kinase family, LIMK1 and LIMK2 are ubiquitously expressed serine kinases that share identical genomic structure and ~ 50% overall identity. The most studied substrate of LIMK1 and LIMK2 is the actin depolymerizing factor (ADF)/cofilin family of proteins. These actin-binding proteins bind to and severe actin filaments (F-actin) and sequester actin monomers resulting in actin depolymerization. Phosphorylation of cofilin by LIMK inhibits its actin-binding activity resulting in the accumulation of F-actin. The actin cytoskeleton plays a pivotal role in the motility of normal cells and in the invasive capacity of tumor cells. Both polymerization and depolymerization of actin are required for cell motility and invasion. Actin polymerization is required at the front of the cell while actin disassembly is required at the rear, effectively moving individual filaments forward using the force generated by polymerization. LIMK1 levels are high in metastatic breast and prostate tumors and in a variety of invasive cancer cell lines. Overexpression of LIMK1 in breast and prostate cancers increased their invasion in vitro and in mice while downregulation of its activity reduced their invasiveness, suggesting that inhibition of LIMK activity with pharmacological agents may be used to inhibit the metastatic spread of cancer cells.

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Acknowledgments

Dr. Bernard’s laboratory is supported by the National Health & Medical Research Council (NHMRC) of Australia, The Cancer Council of Victoria, Australian Research Council Australia, and AICR. Alice Schofield is the recipient of an Australian Postgraduate Award.

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Authors and Affiliations

  1. Department of Medicine, St Vincent’s Institute of Medical Research, Cytoskeleton and Cancer Unit, St. Vincent’s Hospital, The University Melbourne, 9 Princes St, 3065, Fitzroy, VIC, Australia

    Alice Schofield & Ora Bernard Ph.D

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  1. Alice Schofield
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  2. Ora Bernard Ph.D
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Correspondence to Ora Bernard Ph.D .

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Editors and Affiliations

  1. Australia for Medical Research, Iron Metabolism Program, Children's Cancer Institute, Randwick, New South Wales, Australia

    Maria Kavallaris

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Schofield, A., Bernard, O. (2012). LIM Kinase and Cancer Metastasis. In: Kavallaris, M. (eds) Cytoskeleton and Human Disease. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-61779-788-0_8

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