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Record W7161849495 · doi:10.82308/35437

Uncovering novel ShcA signaling networks and their impacts on breast cancer growth and therapeutic resistance

2023· dissertation· en· W7161849495 on OpenAlexaboutno aff
Kathryn Hunt

Bibliographic record

Venuenot available
Typedissertation
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicPI3K/AKT/mTOR signaling in cancer
Canadian institutionsnot available
Fundersnot available
KeywordsBreast cancerAcquired resistanceSignal transducing adaptor proteinDruggabilitySignal transductionTyrosine kinaseCancerDiseaseReceptor tyrosine kinase

Abstract

fetched live from OpenAlex

Breast cancer is the most prevalent cancer in Canadian women, and although many advances have been made, all subtypes of breast cancer can develop therapeutic resistance. One such method of therapeutic resistance can be due to abnormal, or hyperactive receptor tyrosine kinase (RTK) signaling, as seen in HER2+ and basal breast cancers. ShcA is an adaptor protein which facilitates downstream RTK signaling cascades, including the MAPK and PI3K/AKT pathways. When ShcA Y313 cannot be phosphorylated, the resulting tumours demonstrated delayed tumour onset and delayed tumour outgrowth. To understand the mechanisms by which this occurs, BioID was performed on both wildtype and mutant ShcA cell populations. With numerous potential interactors identified, an shRNA screen was conducted to narrow down the most probable interactors. In this thesis, I identify potential novel interactors, including PPP6C and eIF4G2, which may be interacting with ShcA to facilitate these phenotypes. As recurrent disease becomes an ever-increasing concern, the identification of novel protein interactions may highlight new druggable targets to overcome these challenges and provide further insight into the complexities of intracellular signalling

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 score0.006

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 integrity0.0000.000
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 head0.264
Teacher spread0.252 · 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

Citations0
Published2023
Admission routes1
Has abstractyes

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