Dysregulation of integrin-linked kinase (ILK) signaling in colonic polyposis
Open Access
- 27 September 2001
- journal article
- research article
- Published by Springer Nature in Oncogene
- Vol. 20 (43) , 6250-6257
- https://doi.org/10.1038/sj.onc.1204791
Abstract
Mutation of the adenomatous polyposis coli (APC) gene and the subsequent dysregulation of β-catenin are well-documented abnormalities in familial adenomatous polyposis (FAP), as well as sporadic polyposis. Intriguingly, overexpression of the integrin-linked kinase (ILK) has been shown to modulate β-catenin subcellular localization and function. However, the significance of this finding for human carcinogenesis remains unclear. Here, we report the increased biochemical activity and expression of ILK protein in polyps from FAP patients. Furthermore, dramatic increases in ILK immunoreactivity were observed in all abnormal crypts from sporadic polyps, when compared with the normal appearing crypts within the same resected specimens. As sulindac and aspirin are the two most important therapeutic/chemopreventative agents demonstrated in colorectal carcinogenesis, in both humans and animals, further investigation revealed that these non-steroidal anti-inflammatory drugs (NSAIDs) target ILK and ILK-mediated events in vivo. These include inhibition of, both the biochemical activation of ILK, inhibition of serine 9 GSK3β phosphorylation and the enhancement of TCF-4 transcriptional activity. In conclusion, ILK protein hyperexpression appears to be an early event in colonic polyposis. Additionally, ILK signaling is shown to undergo modulation by sulindac (and aspirin) for the first time, indicating that it is likely to be one of the targets affected by these agents in vivo.Keywords
This publication has 38 references indexed in Scilit:
- Inhibition of integrin linked kinase (ILK) suppresses β-catenin-Lef/Tcf-dependent transcription and expression of the E-cadherin repressor, snail, in APC−/− human colon carcinoma cellsOncogene, 2001
- Host cyclooxygenase-2 modulates carcinoma growthJournal of Clinical Investigation, 2000
- Sulindac Inhibits Activation of the NF-κB PathwayJournal of Biological Chemistry, 1999
- Functional Interaction of an Axin Homolog, Conductin, with β-Catenin, APC, and GSK3βScience, 1998
- Constitutive Transcriptional Activation by a β-Catenin-Tcf Complex in APC −/− Colon CarcinomaScience, 1997
- Binding of GSK3β to the APC-β-Catenin Complex and Regulation of Complex AssemblyScience, 1996
- SHORT COMMUNICATION: Sulindac suppresses tumorigenesis in the Min mouseCarcinogenesis: Integrative Cancer Research, 1996
- Regulation of cell adhesion and anchorage-dependent growth by a new β1-integrin-linked protein kinaseNature, 1996
- Identification of FAP Locus Genes from Chromosome 5q21Science, 1991
- Casein kinase II is elevated in solid human tumours and rapidly proliferating non‐neoplastic tissueEuropean Journal of Biochemistry, 1990