Glycolytic reprogramming in cancer cells: PKM2 dimer predominance induced by pulsatile PFK-1 activity
Why this work is in the frame
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Bibliographic record
Abstract
The glycolytic enzyme pyruvate kinase M2 (PKM2) exists in both catalytically inactive dimeric and active tetrameric forms. In cancer cells, PKM2 dimer predominance contributes to tumor growth by triggering glycolytic reprogramming. However, the mechanism that promotes PKM2 dimer predominance over tetramer in cancer cells remains elusive. Here, we show that pulsatile phosphofructokinase (PFK-1) activity results in PKM2 dimer predominance. Mathematical simulations predict that pulsatile PFK-1 activity prevents the formation of PKM2 tetramer even under high levels of fructose-1,6-bisphosphate (FBP), a PKM2 tetramer-promoting metabolite produced by PFK-1. We experimentally confirm these predictions at the single-molecule level by providing evidence for pulsatile PFK-1 activity-induced synchronized dissociation of PKM2 tetramers and the subsequent accumulation of PKM2 dimers under high levels of FBP in HeLa cells. Moreover, we show that pulsatile PFK-1 activity-induced PKM2 dimer predominance also controls cell proliferation. Thus, our study reveals the significance of pulsatile PFK-1 activity in cancer cell metabolism.
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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 it