CSIG-06EGFRvIII REQUIRES OSMR AS A CO-RECEPTOR TO DRIVE GLIOBLASTOMA PATHOGENESIS
Bibliographic record
Abstract
EGFRvIII/STAT3 signaling plays a significant role in glioblastoma pathogenesis. Here, we identify the cytokine receptor OSMR as a direct target gene of the transcription factor STAT3 in mouse astrocytes and human brain tumor stem cells (BTSCs). Strikingly, OSMR forms a receptor complex with EGFRvIII in human BTSCs and mouse astrocytes. Accordingly, gene expression analyses reveal that EGFRvIII, STAT3, and OSMR share a common network of target genes. Interestingly, in astrocytes that do not express EGFRvIII, the ligand OSM stimulates the interaction of OSMR with wild type EGFR, phosphorylation of EGFR, and STAT3 activation. Importantly, knockdown of OSMR strongly suppresses cell proliferation and in vivo tumor growth of EGFRvIII-expressing murine glioblastoma cells and human BTSC xenografts. Our findings define OSMR as a critical regulator of glioblastoma tumor growth that orchestrates a feed forward signaling mechanism with EGFRvIII and STAT3 to drive glioblastoma tumorigenesis.
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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) | 0.001 | 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) | 0.001 | 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; both teacher heads agree on what is shown here.
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".