Inhibition of PAK2 in endothelial cells suppresses tumor angiogenesis and promotes immune sensitization through CXCL10
Bibliographic record
Abstract
ABSTRACT Tumor angiogenesis is induced by the secretion of pro-angiogenic factors and results in a disorganized tumor vasculature. The p21-activated kinase 2 (PAK2) is involved in endothelial cell (EC) migration, an essential step of angiogenesis. However, the involvement of PAK2 in tumor angiogenesis remains ill-defined. Here, we show that, during orthotopic tumor growth, the specific deletion of PAK2 in ECs reduces tumor size and angiogenesis. In addition, endothelial-specific loss of PAK2 was found to normalize the remaining tumor blood vessels, favoring innate immune cells infiltration. Importantly, we uncovered a role for PAK2 in regulating chemokine expression, notably CXCL10. Secretion of CXCL10 from ECs is enhanced following PAK2 depletion and its expression is essential for the inhibitory effects of PAK2 silencing on EC spouting. Furthermore, neutralization of CXCL10 in mice reversed the effects induced by the deletion of PAK2 on tumor vasculature and immune composition of tumors. Together, our findings identify endothelial PAK2 as a potential target to reduce tumor angiogenesis and reprogram ECs to promote immune cell infiltration within tumors through the expression of CXCL10.
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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 | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".