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Record W2800659548 · doi:10.1016/j.celrep.2018.04.019

The Receptor Tyrosine Kinase AXL Is Required at Multiple Steps of the Metastatic Cascade during HER2-Positive Breast Cancer Progression

2018· article· en· W2800659548 on OpenAlexafffund
Marie-Anne Goyette, Stéphanie Duhamel, Léo Aubert, Ariane Pelletier, Paul Savage, Marie‐Pier Thibault, Radia Marie Johnson, Peter Carmeliet, Mark Basik, Louis Gaboury, William J. Muller, Morag Park, Philippe P. Roux, Jean‐Philippe Gratton, Jean‐François Côté

Bibliographic record

VenueCell Reports · 2018
Typearticle
Languageen
FieldImmunology and Microbiology
TopicPhagocytosis and Immune Regulation
Canadian institutionsMcGill UniversityJewish General HospitalInstitute for Research in Immunology and CancerMcGill University Health CentreUniversité de MontréalMontreal Clinical Research Institute
FundersFonds de Recherche du Québec - SantéCanadian Institutes of Health ResearchFondation du cancer du sein du QuébecMcGill University
KeywordsGAS6AXL receptor tyrosine kinaseIntravasationMetastatic breast cancerBreast cancerCancer researchReceptor tyrosine kinaseMetastasisCancerMedicineExtravasationTrastuzumabOncologyInternal medicineReceptorPathology

Abstract

fetched live from OpenAlex

AXL is activated by its ligand GAS6 and is expressed in triple-negative breast cancer cells. In the current study, we report AXL expression in HER2-positive (HER2 + ) breast cancers where it correlates with poor patient survival. Using murine models of HER2 + breast cancer, Axl, but not its ligand Gas6, was found to be essential for metastasis. We determined that AXL is required for intravasation, extravasation, and growth at the metastatic site. We found that AXL is expressed in HER2 + cancers displaying epithelial-to-mesenchymal transition (EMT) signatures where it contributes to sustain EMT. Interfering with AXL in a patient-derived xenograft (PDX) impaired transforming growth factor β (TGF-β)-induced cell invasion. Last, pharmacological inhibition of AXL specifically decreased the metastatic burden of mice developing HER2 + breast cancer. Our data identify AXL as a potential anti-metastatic co-therapeutic target for the treatment of HER2 + breast cancers.

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 machine prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.005

Distilled classifier scores by category (both heads)

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 communication0.0010.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0020.000

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.

Opus teacher head0.011
GPT teacher head0.256
Teacher spread0.245 · 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 source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
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

Citations144
Published2018
Admission routes2
Has abstractyes

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