Integrin-linked kinase links dynactin-1/dynactin-2 with cortical integrin receptors to orient the mitotic spindle relative to the substratum.

Cells must divide strictly along a plane to form an epithelial layer parallel to the basal lamina. The axis of cell division is primarily governed by the orientation of the mitotic spindle and spindle misorientation pathways have been implicated in cancer initiation. While β1-Integrin and the Dynein/Dynactin complex are known to be involved, the pathways linking these complexes in positioning mitotic spindles relative to the basal cortex and extracellular matrix remain to be elucidated.

Regulation of mitotic cytoskeleton dynamics and cytokinesis by integrin-linked kinase in retinoblastoma cells.

During cell division integrin-linked kinase (ILK) has been shown to regulate microtubule dynamics and centrosome clustering, processes involved in cell cycle progression, and malignant transformation. In this study, we examine the effects of downregulating ILK on mitotic function in human retinoblastoma cell lines. These retinal cancer cells, caused by the loss of function of two gene alleles (Rb1) that encode the retinoblastoma tumour suppressor, have elevated expression of ILK.

Requirement of epithelial integrin-linked kinase for facilitation of Citrobacter rodentium-induced colitis.

Background: Integrin-linked kinase (ILK) is a serine-threonine kinase that transduces extracellular matrix-related cues into intracellular signals, with fundamental roles in cell motility, development and cancer. Recently ILK been shown to have an important role in bacterial epithelial cell attachment, through ILK-bacterial OspE binding. Here we report on the role of epithelial derived ILK in response to Citrobacter rodentium infection.

Role of epithelial integrin-linked kinase in promoting intestinal inflammation: effects on CCL2, fibronectin and the T cell repertoire.

Background: The role of integrin signaling in mucosal inflammation is presently unknown. Hence, we aimed to investigate the role of epithelial-derived integrin-linked kinase (ILK), a critical integrin signaling intermediary molecule, in colonic inflammation.

Methods: Conditional intestinal epithelial cell ILK knockout mice were used for assessment of acute and chronic dextran sodium sulfate (DSS)-induced colitis.

Cutting edge: PHLPP regulates the development, function, and molecular signaling pathways of regulatory T cells.

Regulatory T cells (Tregs) have a reduced capacity to activate the PI3K/Akt pathway downstream of the TCR, and the resulting low activity of Akt is necessary for their development and function. The molecular basis for the failure of Tregs to activate Akt efficiently, however, remains unknown. We show that PH-domain leucine-rich-repeat protein phosphatase (PHLPP), which dephosphorylates Akt, is upregulated in Tregs, thus suppressing Akt activation.

The importance of integrin-linked kinase in the regulation of bladder cancer invasion.

It is important to understand the molecular mechanisms of bladder cancer progression not only to prevent cancer progression but also to detect new therapeutic targets against advanced bladder cancer. The integrin-linked kinase (ILK) is a major signaling integrator in mammalian cells and plays an important role in epithelial-mesenchymal transition (EMT) of human cancers, but its mechanisms are not completely understood. In this study, we investigated the importance and mechanisms of ILK in bladder cancer progression.

The single IgG IL-1-related receptor controls TLR responses in differentiated human intestinal epithelial cells.

Intestinal epithelial cells (IECs) are constantly exposed to enteric microbes. Although IECs express TLRs that recognize bacterial products, the activation of these TLRs is strictly controlled through poorly understood mechanisms, producing a state of hyporesponsiveness and preventing unwanted inflammation. The single IgG IL-1-related receptor (Sigirr) is a negative regulator of TLRs that is expressed by IECs and was recently shown to inhibit experimental colitis.

Tumor expression of integrin-linked kinase (ILK) correlates with the expression of the E-cadherin repressor snail: an immunohistochemical study in ductal pancreatic adenocarcinoma.

Integrin-linked kinase (ILK) is a key molecule involved in mediating several biological functions including cell-matrix interactions, angiogenesis, and invasion, as well as playing a role in epithelial to mesenchymal transition (EMT) in cancer cells. In ductal pancreatic adenocarcinoma, increased expression of ILK has been linked to tumor prognosis and correlated with increased chemoresistance to drugs, such as gemcitabine. However, the precise relationship between ILK, Snail, E-cadherin, and N-cadherin expression on the stepwise development of pancreatic cancer is unknown.

Expression of integrin-linked kinase is not a useful prognostic marker in resected hepatocellular cancer.

Background: Hepatocellular cancer (HCC) is one of the most common malignancies worldwide, and is known to be associated with a poor prognosis. Unfortunately there are no available reliable markers of prognosis. The aim of this study was to determine whether integrin-linked kinase (ILK) expression correlates with post-resection survival from HCC.

Investigation of interleukin 1beta-mediated regulation of NF-kappaB activation in colonic cells reveals divergence between PKB and PDK-transduced events.

Recent work has highlighted a role for PDK1 in adaptive immunity, however its contribution to innate immunity has not been addressed. We have investigated the role of PKB and PDK1 in IL-1beta-induced NF-kappaB activation. Over-expression of either in HCT 116 and HEK 293T cells, effected a reproducible NF-kappaB activation.

The specific JNK inhibitor SP600125 targets tumour necrosis factor-alpha production and epithelial cell apoptosis in acute murine colitis.

Stress-activated protein kinases (SAPKs) are activated in human inflammatory bowel disease (IBD). Recently it has been demonstrated that p38MAPK (mitogen-activated protein kinase) inhibition using SB203580 is effective in reducing disease in both dextran sulphate sodium (DSS)-induced and 2,4,6-trinitrobenzenesulphonic acid (TNBS)-induced murine colitides, underscoring the importance of this pathway in gastrointestinal inflammation. However, the contribution of c-Jun N-terminal kinase (JNK) in intestinal inflammation is unknown.

Curcumin mediates ceramide generation via the de novo pathway in colon cancer cells.

A wealth of evidence supports the notion that curcumin, a phytochemical present in turmeric, is a potent chemopreventive agent for colon cancer. Its mechanism of action remains incompletely understood. Here we report that curcumin's apoptosis-inducing effects in colon cancer cell lines are accompanied by robust ceramide generation.