4.5 Review

Integrin-linked kinase - essential roles in physiology and cancer biology

Journal

JOURNAL OF CELL SCIENCE
Volume 121, Issue 19, Pages 3121-3132

Publisher

COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/jcs.017996

Keywords

cancer; development; extracellular matrix; integrin-linked kinase; protein-protein interaction; signal transduction

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Funding

  1. National Cancer Institute of Canada
  2. Terry Fox Foundation
  3. Canadian Breast Cancer Research Alliance
  4. Canadian Breast Cancer Foundation and the Cancer Research Society

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Integrin-linked kinase (ILK) is a multifunctional intracellular effector of cell-matrix interactions and regulates many cellular processes, including growth, proliferation, survival, differentiation, migration, invasion and angiogenesis. The use of recently developed Cre-lox-driven recombination and RNA-interference technologies has enabled the evaluation of the physiological roles of ILK in several major organ systems. Significant developmental and tissue-homeostasis defects occur when the gene that encodes ILK is deleted, whereas the expression of ILK is often elevated in human malignancies. Although the cause(s) of ILK overexpression remain to be fully elucidated, accumulating evidence suggests that its oncogenic capacity derives from its regulation of several downstream targets that provide cells with signals that promote proliferation, survival and migration, supporting the concept that ILK is a relevant therapeutic target in human cancer. Furthermore, a global analysis of the ILK 'interactome' has yielded several novel interactions, and has revealed exciting and unexpected cellular functions of ILK that might have important implications for the development of effective therapeutic agents.

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