The role of integrin-linked kinase (ILK) in cancer progression

被引:169
作者
Persad, S
Dedhar, S [1 ]
机构
[1] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada
[2] Hamilton Reg Canc Ctr, Hamilton, ON L8V 1C3, Canada
[3] McMaster Univ, Hamilton, ON, Canada
[4] Univ British Columbia, Dept Biochem, Vancouver, BC, Canada
关键词
integrins; PKB/Akt; cell survival; tumorigenesis; EMT; therapeutics;
D O I
10.1023/A:1023777013659
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Integrin-linked kinase (ILK) is an intracellular protein, which interacts with the cytoplasmic domains of integrin beta1 and beta3 subunits. ILK is a 59 kDa protein containing a phosphoinositide phospholipid-binding domain flanked by an N-terminal ankyrin repeat domain and a C-terminal serine/threonine protein kinase domain. Genetic and biochemical evidence have established an essential role of ILK in connecting integrins to the actin cytoskeleton. Apart from integrins, ILK interacts with several adaptor and signaling proteins resulting in its activation and localization to focal adhesion plaques. The kinase activity of ILK is stimulated upon integrin engagement, as well as by growth factors and chemokines in a PI-3Kinase-dependent manner. ILK can mediate the phosphorylation of a variety of intracellular substrates, most notable of which are: protein kinase B (PKB/Akt), glycogen synthase kinase-3 (GSK-3) and myosin light chain. Gain and loss of function strategies have shown that overexpression, and/or constitutive activation of ILK results in oncogenic transformation and progression to invasive and metastatic phenotypes. In addition ILK expression and activity are upregulated in several types of cancers. In this review, we summarize the adaptor and signaling properties of ILK, and also progress in the identification of therapeutic strategies for inhibition of ILK activity.
引用
收藏
页码:375 / 384
页数:10
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