The Role of VHL in the Regulation of E-Cadherin: A New Connection in an Old Pathway
Bibliographic record
Abstract
The von Hippel-Lindau (VHL) protein is a critical regulator of the ubiquitous oxygen-sensing pathway. VHL is a component of an E3 ubiquitin ligase that targets the alpha subunit of hypoxia-inducible factor (HIFalpha) for ubiquitin-mediated destruction under normal oxygen tension. As a consequence of HIFalpha stabilization upon the functional loss of VHL, the cell constitutively upregulates the hypoxic program resulting in the inappropriate expression of genes responsible for global changes in angiogenesis, energy metabolism, and proliferation. The emerging evidence suggests that the inactivation of VHL-HIF pathway is critical for the development of clear-cell renal cell carcinoma (CC-RCC). Until recently, the downstream effector(s) of HIF responsible for the oncogenic transformation of renal epithelial cells remained largely unknown. This review highlights recent discoveries uncovering the transcriptional regulation of E-cadherin, a homophilic cell adhesion molecule with anti-invasive properties in numerous epithelial-derived cancers, via the VHL-HIF pathway.
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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) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.002 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".