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Record W3029073942 · doi:10.1101/764944

GLUT1 inhibition blocks growth of RB1-positive Triple Negative Breast Cancer

2019· preprint· en· W3029073942 on OpenAlexafffund
Qin Wu, Wail Ba-Alawi, Geneviève Deblois, Jennifer Cruickshank, Shili Duan, Evelyne Lima‐Fernandes, Jillian Haight, Seyed Ali Madani Tonekaboni, Anne-Marie Fortier, Hellen Kuasne, Trevor D. McKee, Hassan Mahmoud, Sarina Cameron, Nergiz Doğan, Wenjun Chen, Ravi N. Vellanki, Stanley Zhou, Susan J. Done, Morag Park, David W. Cescon, Benjamin Haibe‐Kains, Mathieu Lupien, C.H. Arrowsmith

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2019
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicCancer, Hypoxia, and Metabolism
Canadian institutionsVector InstitutePublic Health OntarioOccupational Cancer Research CentreCancer Care OntarioMcGill University Health CentreStructural Genomics ConsortiumPrincess Margaret Cancer CentreOntario Institute for Cancer ResearchUniversity of TorontoUniversity Health Network
FundersCanadian Institutes of Health ResearchGovernment of OntarioOntario Institute for Cancer ResearchNovartis PharmaOntario Genomics InstituteEuropean Federation of Pharmaceutical Industries and AssociationsMerck KGaAMcGill University Health CentreOntario Ministry of Research, Innovation and ScienceOntario GenomicsFundação de Amparo à Pesquisa do Estado de São PauloGenome CanadaTerry Fox Research InstituteCancer Research SocietyPrincess Margaret Cancer FoundationPfizer
KeywordsTriple-negative breast cancerGLUT1Cancer researchBreast cancerCancerGlucose transporterRetinoblastomaMedicineBiologyInternal medicineGeneBiochemistry

Abstract

fetched live from OpenAlex

Abstract Triple negative breast cancer (TNBC) is a deadly form of breast cancer due to the development of resistance to chemotherapy affecting over 30% of patients. New therapeutics and companion biomarkers are urgently needed. Recognizing the elevated expression of glucose transporter 1 (GLUT1, encoded by SLC2A1 ) and associated metabolic dependencies in TNBC, we investigated the vulnerability of TNBC cell lines and patient-derived samples to GLUT1 inhibition. We report that genetic or pharmacological inhibition of GLUT1 with BAY-876 impairs the growth of a subset of TNBC cells displaying high glycolytic and lower oxidative phosphorylation (OXPHOS) rates. Pathway enrichment analysis of gene expression data implicates E2F Targets pathway activity as a surrogate of OXPHOS activity. Furthermore, the protein levels of retinoblastoma tumor suppressor (RB1) are strongly correlated with the degree of sensitivity to GLUT1 inhibition in TNBC, where RB1-negative cells are insensitive to GLUT1 inhibition. Collectively, our results highlight a strong and targetable RB1-GLUT1 metabolic axis in TNBC and warrant clinical evaluation of GLUT1 inhibition in TNBC patients stratified according to RB1 protein expression levels.

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 score0.003
Threshold uncertainty score0.008

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 communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0030.001

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 head0.007
GPT teacher head0.215
Teacher spread0.208 · 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

Citations19
Published2019
Admission routes2
Has abstractyes

Explore more

Same venuebioRxiv (Cold Spring Harbor Laboratory)Same topicCancer, Hypoxia, and MetabolismFrench-language works237,207