Translation initiation: a critical signalling node in cancer
Bibliographic record
Abstract
Mammalian target of rapamycin (mTOR) is a master regulator of translation initiation that controls the recruitment of ribosomes to mRNA templates in response to intracellular and extracellular cues. Evidence suggests that mTOR and its direct downstream targets, S6K and eIF4E/4E-BP, play significant roles in oncogenesis, and that inhibiting this pathway holds promise as an anti-proliferative approach. Recent genome-wide analyses of mutations in human cancers indicate that transformed cells activate a handful of processes and signalling pathways that are major contributors to their phenotype. Here we review the current literature implicating mTOR and translation initiation downstream of many of these various signalling pathways and processes usurped in human cancers. This review highlights the widespread activation of mTOR/eIF4E following acquisition of oncogenic lesions and its implication in promoting the transformation phenotype and indicates that targeting the control of translation initiation makes logical sense as a broad-acting therapeutic approach.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.000 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.002 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 0.005 |
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".