Understanding the Regulation of HMGCR
Bibliographic record
Abstract
Statins inhibit 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), the rate limiting enzyme of the mevalonate (MVA) pathway, and are also known to possess tumour-specific apoptotic effects. This tumour-specific statin-sensitivity can be defined on the basis of features such as dysregulation of the MVA pathway. We show that a subset of lung cancer cell lines undergo statin-induced apoptosis. We next address whether sensitivity is associated with HMGCR dysregulation at the level of post-translational modification. We focus on the key residue S872, which has been shown to be phosphorylated by AMP-activated protein kinase (AMPK) in vitro. We show that this site does not affect proliferation rate in two cell lines, and demonstrate that it significantly reduces anchorage independent growth in one cell system. In summary, we show that a subset of lung cancer cell lines are sensitive to statin-induced apoptosis and begin to understand whether HMGCR dysregulation may be a hallmark of statin-sensitivity.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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 teacher head, 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".