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Record W2796694477 · doi:10.1101/283309

The ERBB-STAT3 Axis Drives Tasmanian Devil Facial Tumor Disease

2018· preprint· en· W2796694477 on OpenAlexaff
Lindsay Kosack, Bettina Wingelhofer, Alexandra Popa, Bojan Vilagos, Anna Orlova, Peter Májek, Katja Parapatics, Alexander Lercher, Benedikt Agerer, Anna Ringler, Johanna Klughammer, Mark Smyth, Kseniya Khamina, Hatoon Baazim, David A. Rosa, Jisung Park, Patrick T. Gunning, Christoph Bock, Hannah V. Siddle, Stefan Kubicek, Elizabeth P. Murchison, Keiryn L. Bennett, Richard Moriggl, Andreas Bergthaler

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2018
Typepreprint
Languageen
FieldMedicine
TopicVeterinary Oncology Research
Canadian institutionsUniversity of Toronto
FundersAustrian Science FundÖsterreichische ForschungsförderungsgesellschaftÖsterreichischen Akademie der Wissenschaften
KeywordsBiologyErbBCancer researchImmunosurveillanceReceptor tyrosine kinaseMHC class IMajor histocompatibility complexSignal transductionImmunologyCell biologyImmune systemTumor cells

Abstract

fetched live from OpenAlex

Summary The marsupial Tasmanian devil ( Sarcophilus harrisii ) faces extinction due to transmissible devil facial tumor disease (DFTD). To unveil the molecular underpinnings of DFTD, we designed an approach that combines sensitivity to drugs with an integrated systems-biology characterization. Sensitivity to inhibitors of the ERBB family of receptor tyrosine kinases correlated with their overexpression, suggesting a causative link. Proteomic and DNA methylation analyses revealed tumor-specific signatures linked to oncogenic signaling hubs including evolutionary conserved STAT3. Indeed, ERBB inhibition blocked phosphorylation of STAT3 and arrested cancer cells. Pharmacological blockade of ERBB signaling prevented tumor growth in a xenograft model and resulted in recovery of MHC class I gene expression. This link between the hyperactive ERBB-STAT3 axis and MHC class I mediated tumor immunosurveillance provides mechanistic insights into horizontal transmissibility and led us to the proposition of a dual chemo-immunotherapeutic strategy to save Tasmanian devils from DFTD.

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.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow), Insufficient payload (model declined to judge)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.677
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.001
Science and technology studies0.0010.001
Scholarly communication0.0000.000
Open science0.0010.002
Research integrity0.0000.002
Insufficient payload (model declined to judge)0.0000.001

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.

Opus teacher head0.027
GPT teacher head0.291
Teacher spread0.263 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designObservational
Domainnot available
GenreEmpirical

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".

Quick stats

Citations5
Published2018
Admission routes1
Has abstractyes

Explore more

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