Valine Catabolism Drives Bioenergetic and Lipogenic Fuel Plasticity in Prostate Cancer
Bibliographic record
Abstract
Abstract Metabolic reprogramming is a hallmark of cancer and fundamental for disease progression. The remodelling of oxidative phosphorylation and enhanced lipogenesis are key characteristics of prostate cancer (PCa). Recently, succinate-dependent mitochondrial reprogramming was identified in high-grade prostate tumours with upregulation of enzymes associated with branched-chain amino acid (BCAA) catabolism. We hypothesised that the degradation of BCAAs, particularly valine may play a critical role in anapleurotic refuelling of the mitochondrial succinate pool. Through suppression of valine availability, we report strongly reduced lipid content despite compensatory upregulation of fatty acid uptake, indicating valine is an important lipogenic fuel in PCa. Inhibition of the enzyme 3-hydroxyisobutyryl-CoA hydrolase (HIBCH) also resulted in selective inhibition of cellular proliferation of malignant but not benign prostate cells and impaired succinate production. In combination with a comprehensive multi-omic investigation of patient and cell line data, our work highlights a therapeutic target for selective inhibition of metabolic reprogramming in PCa.
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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) | 0.001 | 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 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".