Abstract 2374: Integrin-linked kinase (ILK) promotes melanoma angiogenesis by activating IL-6 signaling pathway
Bibliographic record
Abstract
Abstract Integrin-linked kinase (ILK) is a highly conserved serine-threonine protein kinase involved in cell-ECM interactions, cytoskeletal organization, and cell signaling. Overexpression of ILK in epithelial cells leads to anchorage-independent growth with increased cell cycle progression. Previously, we have shown that ILK upregulation strongly correlates with melanoma progression, invasion and inversely correlates with 5-year survival of melanoma patients. We also found that ILK knockdown impeded melanoma cell migration, invasion and impaired the growth of melanoma xenografts in severe combined immunodeficient (SCID) mice. However, the molecular mechanism by which ILK enhances melanoma angiogenesis is currently unknown. In the present study, we found that pro-angiogenic molecule interleukin-6 (IL-6) is the downstream transcriptional target of ILK in melanoma cells. ILK overexpression increased IL-6 whereas shRNA mediated silencing of ILK suppressed IL-6 expression both transcriptionally and translationally. By electromobility shift assays, we found that ILK enhanced the binding of transcription factor (NF-κB) to IL-6 promoter and this binding was reduced in ILK knockdown cells. Furthermore, Conditioned media (CM) from ILK- overexpressing cells enhanced the tube forming ability of HUVEC cells in vitro. This tube formation by HUVEC cells was IL-6 dependent as CM from IL6-siRNA treated ILK-overexpressing melanoma cells inhibited the tube formation of HUVEC cells. In order to delineate the mechanism by which ILK-upregulated IL-6 can enhance the growth of endothelial cells, further analysis of the downstream targets of IL-6 signaling showed an increase in activity and nuclear translocation of STAT3 in ILK-overexpressing cells. As STAT3 binds to VEGF promoter, we found that VEGF levels were elevated in ILK-overexpressing cells and declined in ILK knockdown cells, suggesting that ILK may regulate VEGF expression through IL-6 pathway by upregulating and activating STAT3. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2374.
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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 | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 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".