Abstract 2989: Integrin-linked kinase regulates mitotic spindle dynamics and its overexpression leads to resistance to paclitaxel-induced cell death
Bibliographic record
Abstract
Abstract Dysregulated mitosis is a hallmark of cancer. Many centrosomal proteins, including the integrin-linked kinase (ILK), that regulate microtubule organization and mitotic spindle assembly have been implicated in cancers. Inhibition or depletion of ILK result in a mitotic spindle defect that has not been well characterized and while ILK is overexpressed in many cancers, the effect of ILK overexpression on mitotic spindle function is unknown. In this study, we have characterized the defective spindle phenotype, and also looked at the effect of ILK overexpression on mitotic spindle function. HeLa cells stably over-expressing wild-type ILK were used for overexpression studies while parental HeLa cells were treated with QLT-0267, an ILK-specific inhibitor, to study the defective spindle phenotype. While ILK inhibition led to an abnormal mitotic spindle phenotype, the spindle contained bona fide kinetochore-microtubules that persisted after cold- or calcium-treatment. ILK inhibition, however, led to higher sister-centromere stretch in chromosomes aligned between two spindle poles, suggesting that kinetochores were under abnormally high tension, likely due to inhibition of microtubule polymerization. Microtubule regrowth in mitotic cells after cold depolymerization was significantly slower with ILK inhibition. In the context of ILK overexpression in cancers, we first measured the duration of mitosis and showed that ILK-overexpressing cells completed mitosis at a faster rate and also required shorter durations between metaphase and anaphase. ILK overexpression also resulted in increased resistance to paclitaxel-induced cell death. Collectively, our data suggest that ILK regulates microtubule dynamics, which is the focus of ongoing investigations in our laboratory, and ILK overexpression has clinical implications by inducing resistance to paclitaxel, possibly through increased microtubule dynamics. This work was supported by funding from the Canadian Institutes of Health Research. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2989. doi:10.1158/1538-7445.AM2011-2989
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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) | 0.002 | 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".