Acquired Capabilities of Cancer Cells Intersect at ADAM17 (TACE)
Bibliographic record
Abstract
Autocrine signalling is a key feature in human cancer that allows tumour cells to proliferate and invade surrounding tissues independent of external cues. Here we demonstrate that the stable silencing of a single protease, ADAM17, is sufficient to abrogate several malignant phenotypes in clear cell renal carcinoma (RCC), a highly invasive human cancer. Silencing ADAM17 limits the availability of soluble transforming growth factor‐alpha (TGFα), an epidermal growth factor receptor (EGFR) ligand, thereby preventing EGFR activation and the establishment of this autocrine growth stimulatory loop. Moreover, inhibiting ADAM17 impedes tumour inflammation, survival, migration and invasion, and abolishes tumour formation in vivo . These data show that ligand‐shedding is a critical step in EGFR activation and they reveal that targeting one biologically relevant enzyme is sufficient to abrogate several fundamental tumour‐promoting features. The full therapeutic consequence of targeting ADAM17 in the treatment of cancer will be discussed here.
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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) | 0.002 | 0.001 |
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".