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Record W4293199696 · doi:10.1101/2022.08.24.505130

On the therapeutic potential of MAPK4 in triple-negative breast cancer

2022· preprint· en· W4293199696 on OpenAlexafffund
Fadia Boudghene-Stambouli, Mathilde Soulez, Natalia Ronkina, Anneke Doerrie, Alexey Kotlyarov, Ole Morten Seternes, Matthias Gaestel, Sylvain Meloche

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2022
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicMelanoma and MAPK Pathways
Canadian institutionsUniversité de MontréalInstitute for Research in Immunology and Cancer
FundersHelse Nord RHFDeutsche ForschungsgemeinschaftCancer Research SocietyKreftforeningen
KeywordsTriple-negative breast cancerPI3K/AKT/mTOR pathwayCancer researchProtein kinase BKinaseSubfamilyCell growthBiologyCancerBreast cancerSignal transductionCell biologyGeneGenetics

Abstract

fetched live from OpenAlex

ERK3/MAPK6 (MAPK6 gene) along with its paralog ERK4/MAPK4 (MAPK4 gene) define a distinct subfamily of atypical mitogen-activated protein kinases (MAPKs). Much remains to be learned about the substrates and biological functions of these signaling enzymes. Interestingly, recent work has suggested that ERK4 promotes prostate cancer progression via the non-canonical activation of AKT/mTOR signaling. In their recent study, Wang et al. report that ERK4 is expressed in a subset of triple-negative breast cancer (TNBC) cell lines and that this expression is critical for AKT activation and for sustaining TNBC cell proliferation in vitro and tumor growth in mice. They also show that depletion of ERK4 sensitizes TNBC cells to phosphatidylinositol-3-kinase (PI3K) inhibitors. They conclude that ERK4 is a promising therapeutic target for TNBC and has potential for combination therapy with PI3K inhibitors. Here, we raise concerns about the cellular models and experimental approaches used in this study, which compromises the conclusions on the oncogenic role of ERK4 in TNBC.

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 score0.004
Threshold uncertainty score0.014

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)0.0040.001

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 head0.011
GPT teacher head0.223
Teacher spread0.212 · 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

Citations1
Published2022
Admission routes2
Has abstractyes

Explore more

Same venuebioRxiv (Cold Spring Harbor Laboratory)Same topicMelanoma and MAPK PathwaysFrench-language works237,207