TY - JOUR

T1 - The mitotic functions of integrin-linked kinase

AU - Fielding, Andrew B.

AU - Dedhar, Shoukat

PY - 2009/6

Y1 - 2009/6

N2 - 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.

AB - 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.

KW - Actins

KW - Animals

KW - Aurora Kinases

KW - Cell Movement

KW - Centrosome

KW - Cytoskeleton

KW - Gene Expression Regulation

KW - Humans

KW - Microtubules

KW - Mitosis

KW - Models, Biological

KW - Protein-Serine-Threonine Kinases

KW - Signal Transduction

KW - Spindle Apparatus

KW - Tubulin

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

KW - Review

U2 - 10.1007/s10555-008-9177-0

DO - 10.1007/s10555-008-9177-0

M3 - Journal article

C2 - 19153670

VL - 28

SP - 99

EP - 111

JO - Cancer Metastasis Reviews

JF - Cancer Metastasis Reviews

SN - 0167-7659

IS - 1-2

ER -