The role of integrin-linked kinase in the regulation of the Wnt signaling pathway
Bibliographic record
Abstract
Proc Amer Assoc Cancer Res, Volume 45, 2004 3932 Wnt pathways are involved in the control of many biological processes by acting through a core set of proteins that are highly conserved in evolution. The Wnt gene family encodes secreted signaling molecules, which play important roles in tumorigenesis and embryonic development. The downstream effect of this pathway is stabilization of the cytoplasmic pool of β-catenin and its nuclear translocation resulting in the regulation of a number of genes that modulate cell fate, proliferation and apoptosis. In addition, activation of integrin-linked kinase (ILK) has also been implicated in the regulation of β-catenin and its nuclear translocation. ILK is an ankyrin repeat containing serine-threonine protein kinase that can interact directly with the cytoplasmic domains of β1 and β3 integrin subunits. Over-expression of ILK has been shown to result in the translocation of β-catenin to the nucleus, formation of a complex between β-catenin and LEF, a high mobility transcription factor, and transcriptional activation by this LEF/β-catenin complex in mammary epithelial cells. Therefore, the downstream effect of both ILK and Wnt signalling pathways is the regulation of genes through activation of LEF/β-catenin transcription complex. In an attempt to determine whether ILK is a required component of the Wnt signaling pathway we have been able to show that molecular and pharmacological inhibition of ILK interferes with Wnt3a-mediated stabilization of β-catenin. In this study stabilization of β-catenin and activation of LEF/β-catenin transcription complex in L and HEK 293 cells was achieved by treatment with Wnt3a condition medium. However, transient transfection of the dominant negative form of ILK, which has a very limited kinase activity, or treatment with ILK inhibitors, which also blocks the kinase activity of ILK resulted in the inhibition of Wnt3a-induced activation of β-catenin demonstrated by western blot and a promoter-reporter luciferase assay. Deregulation of ILK by constitutive activation and/or over-expression has already been shown to inhibit the activity of GSK-3β in mammary epithelial cells. Therefore, these findings suggest that ILK is a required component of the canonical Wnt pathway by working upstream of GSK-3β and possibly as a kinase involved in the hyperphosphorylation of dvl, the downstream component of the Wnt transmembrane receptor. The understanding of the molecular mechanism behind the interaction between these two pathways particularly in cancer progression could lead to identification of novel therapeutic targets.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".