Cell-cell contact dictates life or death decisions following CD95 activation in cancer
Bibliographic record
Abstract
Abstract Cancer cells react to CD95 activation with either apoptotic or tumorigenic responses. Yet, the determinants of these two antithetic reactions are fundamentally not understood. Here, we show that pre-confined CD95L molecules activate apoptosis of cancer cells in-vitro . For particular CD95L pre-confinement, apoptosis activation is most efficient. Surprisingly, in tumor models, the same pre-confinement yields enhanced proliferation of cancer cells. This shift is rooted in cell-cell interactions, as proliferation was also observed in tumorspheres in-vitro . Indeed, proliferation required death-domain tyrosine phosphorylation of CD95 that was facilitated by cell-cell contacts, whereas decreasing the levels of global tyrosine kinase activity favored apoptosis. Altogether, the response to CD95 activation is cell context-dependent and tunable by CD95L pre-confinement, thereby opening therapeutic opportunities in cancer. One Sentence Summary Cell-cell contact tunes tyrosine-kinase activity thereby dictating life or death upon CD95 activation by pre-confined CD95L.
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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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.007 | 0.002 |
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".