Extensive protein S-nitrosylation associated with human pancreatic ductal adenocarcinoma pathogenesis
Bibliographic record
Abstract
NO (nitric oxide)-mediated protein S-nitrosylation has been established as one major signaling mechanism underlying cancer initiation and development, but its roles in PDAC (pancreatic ductal adenocarcinoma) pathogenesis still remain largely unexplored. In this study, we identified 585 unique S-nitrosylation sites among 434 proteins in PDAC patients and PANC-1 cell line by a site-specific proteomics. Larger number of S-nitrosylated proteins were identified in PDAC tissues and PANC-1 cells than adjacent non-cancerous tissues. These S-nitrosylated proteins are significantly enriched in a multitude of biological processes associated with tumorigenesis, including carbohydrate metabolism, cytoskeleton regulation, cell cycle, focal adhesion, adherent junctions, and cell migration. Components of the pancreatic cancer pathway were extensively S-nitrosylated, such as v-raf-1 murine leukemia viral oncogene homolog 1 (Raf-1) and Signal transducer and activator of transcription 3 (STAT3). Moreover, NOS (NO synthase) inhibitor significantly repressed STAT3 S-nitrosylation in PANC-1 cells, which caused significant increase of STAT3 phosphorylation and PANC-1 cell viability, suggesting important roles of protein S-nitrosylation in PDAC development. These results revealed extensive protein S-nitrosylation associated with PDAC pathogenesis, which provided a basis for protein modification-based cancer diagnosis and targeted therapy.
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How this classification was reachedexpand
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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, 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".