Neuropilins are multifunctional coreceptors involved in tumor initiation, growth, metastasis and immunity
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
// Gérald J. Prud’homme 1,2,3 and Yelena Glinka 1 1 Keenan Research Centre in the Li Ka Shing Knowledge Institute of St. Michael’s Hospital, ON, Canada 2 Department of Laboratory Medicine, St. Michael’s Hospital, Toronto, ON, Canada 3 Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada Correspondence: Gérald J. Prud’homme, email: // Keywords : angiogenesis, cancer stem cell, growth factor, neuropilin, semaphorin, TGF-beta, VEGF Received : August 18, 2012, Accepted : September 01, 2012, Published : September 03, 2012 Abstract The neuropilins (Nrps) are multifunctional proteins involved in development, immunity and cancer. Neuropilin-1 (Nrp1), or its homologue neuropilin-2 (Nrp2), are coreceptors that enhance responses to several growth factors (GFs) and other mediators. Nrps are coreceptors for the class 3 semaphorins (SEMA3), involved in axonal guidance, and several members of the vascular endothelial growth factor (VEGF) family. However, recent findings reveal they have a much broader spectrum of activity. They bind transforming growth factor β1 (TGF-β1) and its receptors, hepatocyte growth factor (HGF) and its receptor (cMet), platelet derived growth factor (PDGF) and its receptors, fibroblast growth factors (FGFs), and integrins. Nrps also promote Hedgehog signaling. These ligands and pathways are all relevant to angiogenesis and wound healing. In the immune system, the Nrps are expressed primarily by dendritic cells (DCs) and regulatory T cells (Tregs), and exert mainly inhibitory effects. In cancer, Nrps have been linked to a poor prognosis, which is consistent with their numerous interactions with ligands and receptors that promote tumor progression. We hypothesize that Nrps boost responses by capturing ligands, regulating GF receptor expression, endocytosis and recycling, and possibly also by signaling independently. Importantly, they promote epithelial-mesenchymal transition (EMT), and the survival of cancer stem cells. The recent finding that Nrps bind and internalize cell-penetrating peptides (CPPs) with arginine/lysine-rich C-terminal motifs (C-end rule; e.g., RXXR) is of interest. These CPPs can be coupled to large drugs for cancer therapy. Almost all studies have been preclinical, but findings suggest Nrps are excellent targets for anti-cancer drug development.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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 | 0.001 |
| 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 it