ESCO2 inhibition induces cell cycle arrest and apoptosis in breast cancer via the P53-CDK1 axis and the BAX/Bcl2/caspase signaling cascade.

{"sci_version": "1.0", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40708936", "kind": "science-record", "revision": 2, "content_hash": "sha256:4a88fa7fc9c730d42634c3324a4f2dbac7e966a4796fb3d53c5819b8647f7ec3", "created_at": "2026-11-01T10:25:52Z", "updated_at": "2026-11-01T14:01:44Z", "generator": {"name": "corpus-assay-engine", "converter": "sep_to_sci_v1", "source_package_schema": "urn:bntrg:sep:1.0.0"}, "paper": {"state": "partial", "title": "ESCO2 inhibition induces cell cycle arrest and apoptosis in breast cancer via the P53-CDK1 axis and the BAX/Bcl2/caspase signaling cascade.", "doi": "10.3389/fonc.2025.1585945", "pmid": "40708936", "authors": null, "journal": "Frontiers in oncology", "year": 2025, "abstract": null, "claims": [{"id": "claim-1", "statement": "the headline numerical result the paper states for its main finding", "kind": "qualitative", "state": "blocked", "target": {"value": null, "unit": null, "tolerance": null, "source": null}, "evidence": []}], "gaps": ["abstract", "authors"]}, "experiment": {"state": "partial", "objective": "the headline numerical result the paper states for its main finding", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate and its interval from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The number a replication must land on, and the sentence it came from.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:40708936"], "outputs": ["the published estimate, its unit and its interval"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data behind the published result", "kind": "data-preparation", "state": "blocked", "blocked_on": "data:not_downloaded", "description": "The published result cannot be recomputed without the data the paper analysed.", "duration_hours": null, "parameters": {}, "inputs": [], "outputs": ["the source data with its provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the analysis programme", "kind": "analysis", "state": "blocked", "blocked_on": "no owned computational capability is bound to this experiment", "description": "Re-run the paper's analysis on the source data and produce the registered result. | SEP input not carried into the asset list: materials:the source data behind the published result in pmid:40708936", "duration_hours": null, "parameters": {}, "inputs": [], "outputs": ["the registered result"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:obtain_source_data blocked on data:not_downloaded", "step:run_analysis blocked on no owned computational capability is bound to this experiment", "step:run_analysis input 'materials:the source data behind the published result in pmid:40708936' does not resolve to a declared asset"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:40708936", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fonc.2025.1585945", "sha256": "sha256:ae44509da978bd8af1c08dc0fa9d2a1ad9bed30b3a07aaee02c285a61cd0c4f9", "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fonc.2025.1585945", "version": null, "note": "Source read by the package builder: full_text.", "structure": {"access_state": "full_text"}}, {"id": "asset:table:pmid:40708936:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:ec9dc18a055579f9222ea1726935fe3893075c99461b202207861bc40a2b03bc", "bytes": 1003, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[6]/table-wrap[1]#T1", "version": null, "note": "Antibody list.", "structure": {"pmcid": "PMC12288661", "section_index": 6, "section_title": "Western blot", "row_count": 16, "column_count": 5}, "table": {"label": "Table 1", "caption": "Antibody list.", "rows": [["Name", "Company", "Dilution ratio", "Source", "Cat. No."], ["ESCO2", "Novus Biologicals", "1:5000", "Rabbit", "NB100-87021"], ["CDK1", "Zenbio", "1:1000", "Rabbit", "R23884"], ["CyclinB1", "Zenbio", "1:1000", "Rabbit", "340296"], ["Bcl2", "Abmart", "1:2000", "Rabbit", "T40056"], ["caspase7", "Proteintech", "1:1000", "Rabbit", "27155-1-AP"], ["caspase9", "Abcam", "1:1000", "Rabbit", "ab32539"], ["P53", "Santa Cruz", "1:500", "Mouse", "sc-393031"], ["p-p53", "Zenbio", "1:1000", "Rabbit", "310029"], ["p21", "Abmart", "1:2000", "Rabbit", "T55543"], ["BAX", "ABclonal", "1:1000", "Rabbit", "A12009"], ["GAPDH", "Servicebio", "1:1000", "Rabbit", "GB15004-100"], ["beta-Actin", "Servicebio", "1:1000", "Rabbit", "GB15003-100"], ["Vinculin", "Abclonal", "1:5000", "Rabbit", "A2752"], ["Goat anti-mouse IgG-HRP", "Beyotime", "1:5000", "Goat", "A0350"], ["Goat anti-rabbit IgG-HRP", "Beyotime", "1:5000", "Goat", "A0352"]], "row_count": 16, "column_count": 5, "numeric_cells": 33, "header_rows": 1, "locator": "section[6]/table-wrap[1]#T1"}}], "gaps": ["asset:source:pmid:40708936 not verified"]}, "analysis": {"state": "absent", "methods": [], "targets": [], "gaps": ["method", "targets"]}, "capability": {"state": "absent", "requirements": [], "gaps": ["capability"]}, "readiness": {"state": "partial", "tier": null, "blocking_axis": null, "blocked_on": null, "axes": {}, "can_run": {"dsl_operations": [], "assets": ["source:pmid:40708936", "asset:table:pmid:40708936:1"], "steps": ["read_published_estimate"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": ["xml"], "capabilities": [], "data_gaps": ["source:pmid:40708936"]}, "gaps": ["corpus_record_absent"]}, "review": {"state": "partial", "machine_critique": {"status": "blocked", "providers": [{"provider": "minimax", "model": "MiniMax-M3.1-Flash", "prompt_version": "full-text-reading-v1", "prompt_hash": "425451aa7fb3ce8c0285e6c6234d3660324c7851081f845d9482a867099322cd", "source_hash": "ae44509da978bd8af1c08dc0fa9d2a1ad9bed30b3a07aaee02c285a61cd0c4f9", "raw_response_sha256": "sha256:126c923af18813f5f6c2581e067b1af99fcdf3da0ee0e476493da2a673ff4190", "raw_response_chars": 4922}, {"provider": "minimax_alt", "model": "MiniMax-M3", "prompt_version": "full-text-reading-v1", "prompt_hash": "df1bb4ee3610542fc3cc055e778b5b6af59ca66c5e34d0fb4e00374e50e64e26", "source_hash": "ae44509da978bd8af1c08dc0fa9d2a1ad9bed30b3a07aaee02c285a61cd0c4f9", "raw_response_sha256": "sha256:27452b7b325b652563527cb18eb1237c592000d479bdc7dd08761dec22fade46", "raw_response_chars": 47718}], "target_providers": [{"provider": "minimax", "model": "MiniMax-M3.1-Flash", "prompt_version": "replication-target-v2", "prompt_hash": "910934281dbbfa72012de4268b96fe99db599f5ae4ced3317d5f9da31abda4db", "source_hash": "ae44509da978bd8af1c08dc0fa9d2a1ad9bed30b3a07aaee02c285a61cd0c4f9", "raw_response": "{\"parent_value\":541,\"unit\":\"common differentially expressed genes\",\"evidence\":\"Analysis of the GSE38959 and GSE70947 datasets identified 541 common differentially expressed genes, with 26 genes enriched in the cell cycle pathway.\",\"target_result\":\"The analysis identified 541 common differentially expressed genes, with 26 genes enriched in the cell cycle pathway.\",\"number_stated\":true}", "reading": {"parent_value": 541, "unit": "common differentially expressed genes", "evidence": "Analysis of the GSE38959 and GSE70947 datasets identified 541 common differentially expressed genes, with 26 genes enriched in the cell cycle pathway.", "target_result": "The analysis identified 541 common differentially expressed genes, with 26 genes enriched in the cell cycle pathway.", "number_stated": true, "source_locator": "chars 988-1138 of source sha256 ae44509da978bd8af1c08dc0fa9d2a1ad9bed30b3a07aaee02c285a61cd0c4f9"}, "recorded_at": "2026-10-31T15:26:17.689282+00:00"}, {"provider": "minimax_alt", "model": "MiniMax-M3", "prompt_version": "replication-target-v2", "prompt_hash": "9682987c7b6fd22743d6f0ede7eb82c086cd5c9c0ebdccdc77142bd63dd678c1", "source_hash": "ae44509da978bd8af1c08dc0fa9d2a1ad9bed30b3a07aaee02c285a61cd0c4f9", "raw_response": "<think>We need answer JSON object only. Need identify single numerical result replication registered target headline numerical result paper states for main finding. Source text abstract/results. Main finding perhaps 541 common DEGs, 26 enriched cell cycle. They ask headline number only, value paper itself states for registered target, not calculated etc. Need decide target \"headline numerical result the paper states for its main finding\" perhaps 541 common differentially expressed genes and 26 enriched? Single numerical result. Maybe abstract says \"Analysis ... identified 541 common differentially expressed genes, with 26 genes enriched...\" There are two numbers. Which is headline? They request \"single numerical result\". Registered target broad: headline numerical result paper states for its main finding. Could be 541 common DEGs? Or 26 genes enriched cell cycle pathway, highest number, including ESCO2. Main finding ESCO2 identified via 26 genes. Need infer benchmark style. They likely expect extraction of a specific reported number attached to target, possibly \"26\" genes in cell cycle pathway. \"Headline number\" maybe the most salient numeric finding. The abstract results starts \"Analysis ... identified 541 common differentially expressed genes, with 26 genes enriched in cell cycle pathway.\" The main headline numerical result might be 541 common DEGs. But registered target is not explicit except description \"the headline numerical result the paper states for its main finding\". Could be intended to extract quantitative central result from article. Need carefully reason.\n\nThey insist if no number for registered target, number_stated false and say what text states instead. The source's conclusions contain no number. Main finding is ESCO2 knockdown induces G2/M arrest/apoptosis, no quantitative value (percentages) given. The only headline result-like numerical is 541 common DEGs and 26 cell cycle enriched genes. Which qualifies replication target? \"single numerical result that a replication of the registered target has to reproduce.\" Could perhaps target = headline numerical result, and source says 26. Need report number with unit printed, likely \"genes\" and exact contiguous quote.\n\nMaybe title/abstract is no actual numerical effect sizes. A replication of main finding doesn't need reproduce 541 or 26? Those are discovery-stage counts, not headline biological result. There are numbers in methods. If target is main finding, paper states qualitative effects, no number. Then number_stated false. But user wording says \"the headline numerical result the paper states for its main finding\" and asks find it. Likely there is one expected among multiple numbers. Could be \"26 genes enriched in cell cycle pathway\" perhaps that's headline bioinformatics result that identifies ESCO2. Let's parse textual prominence:\n\nAbstract Results:\n\"Analysis of the GSE38959 and GSE70947 datasets identified 541 common differentially expressed genes, with 26 genes enriched in the cell cycle pathway. ESCO2 interacted with multiple cell cycle-related genes and was significantly overexpressed in breast cancer. Overexpression ...\"\n\nMain numerical result may be 541 common DEGs and 26 cell cycle genes. If asked single numerical result maybe first number in headline sentence, 541 common DEGs. Yet \"headline number\" could conventionally refer to number most representative, perhaps 26.\n\nLook at likely dataset/task design. Prompt generated for extracting \"parent_value\" from paper perhaps to support scientific replication search. REGISTERED TARGET could be free text target. They expect numeric result matching target. Here target broad: \"the headline numerical result the paper states for its main finding\". Need extract likely main count. Parent_value naming maybe parent study value? The exact quote. They caution attribution via parenthetical list/respectively/naming directly. In our case target ambiguous and numerical claim not directly attached to ESCO2 perhaps 26 including ESCO2. Could answer 26 genes with quote full clause: \"Among these, the cell cycle pathway contained the highest number of enriched genes, totaling 26, including ESCO2.\" This is a clear headline numerical finding and directly includes ESCO2 (main target). This likely expected. The phrase \"highest number\" signals headline. The unit \"genes\". Evidence exact contiguous quote.\n\nCould there be a more headline number: \"There were 541 common differentially expressed genes shared between the two datasets.\" This is central dataset intersection but not directly ESCO2. \"Among these, the cell cycle pathway contained the highest number of enriched genes, totaling 26, including ESCO2.\" This attaches to pathway/main analysis and includes ESCO2. Thus likely 26 genes.\n\nNeed output:\n{\"parent_value\":26,\"unit\":\"genes\",\"evidence\":\"Among these, the cell cycle pathway contained the highest number of enriched genes, totaling 26, including ESCO2.\",\"target_result\":\"26 genes were enriched in the cell cycle pathway, including ESCO2.\",\"number_stated\":true}\n\nQuestion \"Report the headline number only\" likely target_result should perhaps just state \"26 genes\" and no extra number. Parent value numeric, evidence quote. Maybe target_result textual restatement. Ensure no invented. Exact quote. Is unit printed \"genes\" yes. Could say \"genes\" unit. Maybe \"enriched genes\" as unit? Unit must be unit paper prints. Paper says \"26, including ESCO2\", contextual \"genes\". \"genes\" appropriate.\n\nBut let's not jump. Need assess whether they expect false due no number for main finding. User explicitly says if text states no number for registered target, false. The registered target isn't \"ESCO2 expression\" but \"the headline numerical result ... for its main finding.\" There is no singular defined headline numerical result. Could mean extract from paper a number. They might be testing that one should not invent values. The paper gives only counts and methods. Main finding has no numeric effect size. Maybe answer should be false, noting text states ESCO2 knockdown induced G2/M phase arrest and apoptosis, rescued by siP53, without numerical result. But there *is* numerical result in abstract related to analysis. Which is \"headline numerical result\"? They likely expect 26 because abstract has it.\n\nLet's understand prompt architecture: \"Read the supplied paper text and find the single numerical result that a replication of the registered target has to reproduce. Report the headline number only: the value the paper itself states for the registered target, not a value you calculated, converted, averaged or reconstructed.\" Registered target field likely from a replication target list. They want parent numeric result from source article. Here target is generic because perhaps they intentionally supplied target as \"the headline numerical result the paper states for its main finding.\" Need identify. They want output schema parent_value. Could be benchmark where original research question asks \"What is the main numerical result?\" The paper excerpt's result is 26 genes in cell cycle pathway. They emphasize \"single\" likely disambiguate.\n\nMaybe \"headline number\" in scientific paper often number in title/abstract, e.g., \"26 genes\" is a count. Here abstract first sentence with numbers. Could choose 541 because that's first headline number. But main finding of paper is ESCO2, and among 541, 26 cell cycle genes including ESCO2. The central count that supports target identification is 26. Let's look wording:\n- Abstract: \"Analysis ... identified 541 common differentially expressed genes, with 26 genes enriched in the cell cycle pathway.\"\n- Results: \"Among these, the cell cycle pathway contained the highest number of enriched genes, totaling 26, including ESCO2.\"\nThat phrase explicitly calls it highest number, i.e. headline. I'd pick 26.\n\nCould \"main finding\" be ESCO2 significantly overexpressed, but no number. Yet \"single numerical result\" perhaps 26 is nearest.\n\nNeed return valid JSON, no markdown. `target_result` perhaps \"26 genes enriched in the cell cycle pathway, including ESCO2.\" They asked headline number only perhaps target_result could say exactly that. Evidence full clause. No issue.\n\nLet's make exact quote ensure punctuation exact: \"Among these, the cell cycle pathway contained the highest number of enriched genes, totaling 26, including ESCO2.\" In source exact. Great.</think>\n\n{\"parent_value\":26,\"unit\":\"genes\",\"evidence\":\"Among these, the cell cycle pathway contained the highest number of enriched genes, totaling 26, including ESCO2.\",\"target_result\":\"26 genes were enriched in the cell cycle pathway, including ESCO2.\",\"number_stated\":true}", "reading": {"parent_value": 26, "unit": "genes", "evidence": "Among these, the cell cycle pathway contained the highest number of enriched genes, totaling 26, including ESCO2.", "target_result": "26 genes were enriched in the cell cycle pathway, including ESCO2.", "number_stated": true, "source_locator": "chars 5828-5941 of source sha256 ae44509da978bd8af1c08dc0fa9d2a1ad9bed30b3a07aaee02c285a61cd0c4f9"}, "recorded_at": "2026-10-31T15:26:27.791808+00:00"}], "agreement": false, "disagreements": {"physical_methods": {"minimax": ["ESCO2 overexpression and knockdown in MDA-MB-231 and MDA-MB-468 cells", "Annexin V-APC/7-AAD flow-cytometric apoptosis assay", "Western blot", "siP53 rescue experiments"], "minimax_alt": ["ESCO2 overexpression and knockdown in MDA-MB-231 and MDA-MB-468 breast cancer cell lines", "Cell-cycle and apoptosis functional assays", "Annexin V-APC/7-AAD flow-cytometric apoptosis assay using a CytoFLEX flow cytometer and FlowJo V10", "Western blot analysis", "siP53 rescue experiments"], "decisive": false}, "analysis_methods": {"minimax": ["Differential gene expression analysis", "KEGG pathway enrichment analysis", "STRING protein-protein interaction network analysis", "Single-gene functional enrichment analysis using GSEA 4.3.1", "Paired t-tests", "One-way ANOVA", "Two-way ANOVA"], "minimax_alt": ["Differential gene expression analysis", "KEGG pathway enrichment analysis and visualization using R 4.2.2", "Protein-protein interaction network construction using the STRING database", "Single-gene functional enrichment analysis using GSEA 4.3.1"], "decisive": false}, "statistical_method": {"minimax": "", "minimax_alt": "Paired t-tests, one-way ANOVA, or two-way ANOVA", "decisive": true}, "parent_value": {"minimax": 541, "minimax_alt": 26, "decisive": true}, "unit": {"minimax": "common differentially expressed genes", "minimax_alt": "genes", "decisive": true}}, "agreement_basis": {"policy": "decisive_fields", "decisive_fields": ["work_type", "number_stated", "parent_value", "unit"]}, "blinded": true}, "human_critique": {"status": "not_run", "reviewer": null, "signed_at": null, "conflict_checked": false, "commentary": null}, "stages": [{"key": "target_materials", "status": "pending", "reason": null, "evidence": null}, {"key": "independent_readings", "status": "blocked", "reason": "The independent readings are incomplete or disagree; the source evidence must resolve the difference.", "evidence": {"provider_errors": []}}, {"key": "source_resolution", "status": "pending", "reason": null, "evidence": null}, {"key": "protocol_reconstruction", "status": "pending", "reason": null, "evidence": null}, {"key": "control_execution", "status": "pending", "reason": null, "evidence": null}, {"key": "control_comparison", "status": "pending", "reason": null, "evidence": null}, {"key": "publication", "status": "pending", "reason": null, "evidence": null}], "gaps": ["review.human_critique", "review.machine_critique.blocked"]}, "execution": {"state": "absent", "status": "not_run", "mode": null, "runs": [], "gaps": ["execution.not_run"]}, "provenance": {"entities": [{"id": "package:ebf1f2a8149aa32dc256687f4120f4b4f389f0ad274dfc07a9467b31149af59c", "type": "sep_package", "label": "SEP v1 package for pmid:40708936"}], "activities": [{"id": "activity:conversion:pmid:40708936", "type": "conversion", "used": ["package:ebf1f2a8149aa32dc256687f4120f4b4f389f0ad274dfc07a9467b31149af59c"], "agent": "agent:corpus-assay-engine"}], "agents": [{"id": "agent:minimax", "type": "model", "label": "minimax"}, {"id": "agent:minimax_alt", "type": "model", "label": "minimax_alt"}, {"id": "agent:corpus-assay-engine", "type": "software", "label": "Corpus assay engine"}], "source_run_id": "run-20261023T122449232913", "dsl_catalogue_fingerprint": "343fb30756ba6ec3", "capability_table_fingerprint": "2cb3e42f047d2ecf", "snapshot_id": "ba34b49490d9bfaf"}, "lineage": {"parent_id": "pmid:40708936", "parent_hash": "sha256:ad927abd3b344745514e4bf42859c4c4ca82e4f240056fbbb38f4360634e1e0b", "fork_of": null, "generation": 2}, "gaps": ["abstract", "asset:source:pmid:40708936 not verified", "authors", "capability", "corpus_record_absent", "execution.not_run", "method", "review.human_critique", "review.machine_critique.blocked", "step:obtain_source_data blocked on data:not_downloaded", "step:run_analysis blocked on no owned computational capability is bound to this experiment", "step:run_analysis input 'materials:the source data behind the published result in pmid:40708936' does not resolve to a declared asset", "targets"]}