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Correlation of ABI1 and PTEN expression during prostate tumor progression.

2022· article· en· W4212871063 on OpenAlexaff
Leszek Kotula, Anita Hryniewicz‐Jankowska, Xiang Li, Katarzyna Augoff, Csaba Papp, Disharee Das, Sonia H.Y. Kung, Ladan Fazli, Tamara Jasmaspishvili, David M. Berman, Fan Zhang, Baylee A. Porter, Aleksander F. Sikorski, Martin Gleave, Vladimir A. Kuznetsov, Gennady Bratslavsky

Bibliographic record

VenueJournal of Clinical Oncology · 2022
Typearticle
Languageen
FieldMedicine
TopicCancer Diagnosis and Treatment
Canadian institutionsQueen's UniversityUniversity of British Columbia
FundersNational Institutes of Health
KeywordsPTENCancer researchProtein kinase BDownregulation and upregulationTumor progressionProstate cancerPI3K/AKT/mTOR pathwayCancerBiologyMedicineSignal transductionInternal medicineCell biologyGene

Abstract

fetched live from OpenAlex

172 Background: Mechanisms of tumor invasion are not well defined. PTEN, a key tumor suppressor frequently inactivated in epithelial cancers, acts as a central node that controls tumor invasion. Despite PI-3 kinase-phospho-Akt pathway activation resulting in enhanced tumor growth, prostate tumors with PTEN loss undergo p53-mediated senescence that restricts tumor invasion. Methods: ABI1 downregulation is associated with epithelial-mesenchymal transition in highly invasive prostate tumors; these tumors frequently loose PTEN; therefore we set to examine genetic interaction of ABI1 and PTEN using novel mouse model of prostate cancer. We analyzed the correlation of ABI1 and PTEN expression in human PCa tumor tissue. Results: Here, using Abi1/Pten KO mouse model we identified a novel mechanism that guards tumor invasion. In Pten-null tumors upregulation of Abi1 leads to sequestration of activated Src kinase. In the absence of Abi1, this regulation is lost leading to activation of non-canonical WNT-SRC-STAT3 axis and enhanced invasion through activation of MMP2 activity. This molecular mechanism explains progression of tumors with Pten loss from PIN to invasive carcinoma upon concomitant Abi1 inactivation. In human tumors with low Abi1 and Pten are associated with aggressive phenotype, biochemical recurrence and metastasis. Conclusions: ABI1 acts as failsafe mechanism in PTEN null tumors by restricting SRC-mediated tumor invasion. ABI1 might have a predictive value in clinical setting in context of PTEN 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 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)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.128
Threshold uncertainty score0.199

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
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)0.0000.000

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 head0.066
GPT teacher head0.460
Teacher spread0.394 · 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.

The models applied no category: nothing in the taxonomy fit this work.
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".

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Citations0
Published2022
Admission routes1
Has abstractyes

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