Integrated in vivo functional screens and multiomics analyses identify α-2,3-sialylation as essential for melanoma maintenance
Bibliographic record
Abstract
Aberrant glycosylation is a hallmark of cancer biology, and altered glycosylation influences multiple facets of melanoma progression. To identify glycosyltransferases, glycans, and glycoproteins essential for melanoma maintenance, we conducted an in vivo growth screen with a pooled short hairpin RNA library of glycosyltransferases, lectin microarray profiling of benign nevus and melanoma samples, and mass spectrometry-based glycoproteomics. We found that α-2,3-sialyltransferases ST3GAL1 and ST3GAL2 and corresponding α-2,3-linked sialosides are up-regulated in melanoma compared to nevi and are essential for melanoma growth. Glycoproteomics revealed that glycoprotein targets of ST3GAL1 and ST3GAL2 are enriched in transmembrane proteins involved in growth signaling, including the amino acid transporter SLC3A2/CD98hc. CD98hc suppression mimicked the effect of ST3GAL1 and ST3GAL2 silencing, inhibiting melanoma cell proliferation. We found that both CD98hc protein stability and its prosurvival effect on melanoma are dependent upon α-2,3-sialylation mediated by ST3GAL1 and ST3GAL2. Our studies reveal α-2,3-sialosides functionally contributing to melanoma maintenance, supporting ST3GAL1 and ST3GAL2 as therapeutic targets in melanoma.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| 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".