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Pivotal role of NAMPT in the switch of melanoma cells toward an invasive and drug-resistant phenotype

2018· article· en· 99 citations· W2791070352 on OpenAlex· 10.1101/gad.305854.117

Why is this work in the frame?

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

Canadian funderA Canadian agency funded it. The work may carry no Canadian affiliation at all.

No Canadian affiliation. An affiliation-only frame, the usual design, would never have seen this work. It is one of the works that make the case for inverting the frame.

Full frame distilled prediction

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.

Candidate categories
none
Consensus categories
none
Domain
Candidate signal: noneConsensus signal: none
Study design
Candidate signal: Bench or experimentalConsensus signal: Bench or experimental
Genre
Candidate signal: EmpiricalConsensus signal: Empirical
Teacher disagreement score
0.283
Threshold uncertainty score
0.309
Validation status
machine_predicted_unvalidated · codex-gemma-dda1882f352a

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

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.

Opus teacher head0.013
GPT teacher head0.245
Teacher spread
0.232 · how far apart the two teachers sit on this one work
Validation status
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

Abstract

In BRAF V600E melanoma cells, a global metabolomic analysis discloses a decrease in nicotinamide adenine dinucleotide (NAD + ) levels upon PLX4032 treatment that is conveyed by a STAT5 inhibition and a transcriptional regulation of the nicotinamide phosphoribosyltransferase (NAMPT) gene. NAMPT inhibition decreases melanoma cell proliferation both in vitro and in vivo, while forced NAMPT expression renders melanoma cells resistant to PLX4032. NAMPT expression induces transcriptomic and epigenetic reshufflings that steer melanoma cells toward an invasive phenotype associated with resistance to targeted therapies and immunotherapies. Therefore, NAMPT, the key enzyme in the NAD + salvage pathway, appears as a rational target in targeted therapy-resistant melanoma cells and a key player in phenotypic plasticity of melanoma cells.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

The record

Venue
Genes & Development
Topic
Sirtuins and Resveratrol in Medicine
Field
Medicine
Canadian institutions
not available
Funders
Institut National Du CancerInstitut National de la Santé et de la Recherche MédicaleUniversité de LilleUniversité de Moncton
Keywords
Nicotinamide phosphoribosyltransferaseMelanomaBiologyNAD+ kinaseCancer researchPhenotypeNicotinamide adenine dinucleotideTranscriptomeEpigeneticsSirtuin 1Downregulation and upregulationGene expressionEnzymeGeneGeneticsBiochemistry
Has abstract in OpenAlex
yes