Pannexin 1 knockdown in metastatic melanoma cells induces cell differentiation into a melanocytic phenotype decreasing tumor size and metastasis in vivo
Bibliographic record
Abstract
Pannexin 1 (Panx1) is a channel‐forming glycoprotein expressed in different cell types of mammalian skin. We studied the role of Panx1 in melanoma tumorigenesis and metastasis since the mouse melanocyte line CRL‐2770 showed low levels of Panx1 expression, while Panx1 in isogenic melanoma cell lines (B16‐F0, ‐F10 and ‐BL6) was increasingly up‐regulated according to qPCR and Western blot assays. Panx1 shRNA knockdown generated stable BL6 cell lines (Panx1‐KD) that showed a marked increase in melanocyte‐like cell characteristics, including higher melanin production, decreased cell migration and enhanced formation of cellular projections, while compromising Panx1 dye uptake channel function. Western blotting and proteomic analyses using 2D‐SDS‐PAGE gels/mass spectroscopy identified vimentin and beta‐catenin as some of the markers of malignant melanoma that were down‐regulated in Panx1‐KD cells. In vivo, Panx1‐KD cells were implanted on chorioallantoic membranes of day 10 avian embryos. After seven days, the excised Panx1‐KD tumors were significantly smaller than controls and metastasis to the liver was significantly reduced as quantified by mouse‐Alu qPCR of the excised embryonic organs. These data suggests that Panx1 may play a role in skin melanocytes that is potentially dysregulated upon malignant transformation in metastatic melanomas. Supported by the Canadian Institutes of Health Research.
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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) | 0.002 | 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 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".