Comparative Proteomics of Dying and Surviving Cancer Cells Improves the Identification of Drug Targets and Sheds Light on Cell Life/Death Decisions.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:29572246", "kind": "science-record", "revision": 2, "content_hash": "sha256:d3051421e4e84ee639646048460f83312e3c25f872705731c8c11161470cec2a", "created_at": "2026-11-01T15:40:32Z", "updated_at": "2026-11-01T18:49:24Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Comparative Proteomics of Dying and Surviving Cancer Cells Improves the Identification of Drug Targets and Sheds Light on Cell Life/Death Decisions.", "doi": "10.1074/mcp.RA118.000610", "pmid": "29572246", "authors": ["Amir Ata Saei", "Pierre Sabatier", "Ülkü Güler Tokat", "Alexey Chernobrovkin", "Mohammad Pirmoradian", "Roman A Zubarev"], "journal": "Molecular & cellular proteomics : MCP", "year": 2018, "abstract": "Chemotherapeutics cause the detachment and death of adherent cancer cells. When studying the proteome changes to determine the protein target and mechanism of action of anticancer drugs, the still-attached cells are normally used, whereas the detached cells are usually ignored. To test the hypothesis that proteomes of detached cells contain valuable information, we separately analyzed the proteomes of detached and attached HCT-116, A375, and RKO cells treated for 48 h with 5-fluorouracil, methotrexate and paclitaxel. Individually, the proteomic data on attached and detached cells had comparable performance in target and drug mechanism deconvolution, whereas the combined data significantly improved the target ranking for paclitaxel. Comparative analysis of attached versus detached proteomes provided further insight into cell life and death decision making. Six proteins consistently up- or downregulated in the detached versus attached cells regardless of the drug and cell type were discovered; their role in cell death/survival was tested by silencing them with siRNA. Knocking down USP11, CTTN, ACAA2, and EIF4H had anti-proliferative effects, affecting UHRF1 additionally sensitized the cells to the anticancer drugs, while knocking down RNF-40 increased cell survival against the treatments. Therefore, adding detached cells to the expression proteomics analysis of drug-treated cells can significantly increase the analytical value of the approach. The data have been deposited to the ProteomeXchange with identifier PXD007686.", "claims": [{"id": "claim-target-result", "statement": "The combined attached-and-detached proteomic data significantly improved target ranking for paclitaxel; no specific statistical method is named in the abstract, and the source data were deposited in ProteomeXchange under identifier PXD007686.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:29572246", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Individually, the proteomic data on attached and detached cells had comparable performance in target and drug mechanism deconvolution, whereas the combined data significantly improved the target ranking for paclitaxel."}, {"asset": "source:pmid:29572246", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "The data have been deposited to the ProteomeXchange with identifier PXD007686."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "The combined attached-and-detached proteomic data significantly improved target ranking for paclitaxel; no specific statistical method is named in the abstract, and the source data were deposited in ProteomeXchange under identifier PXD007686.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:29572246"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "blocked", "blocked_on": "data:accession_absent", "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": [], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": [], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:obtain_source_data blocked on data:accession_absent"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:29572246", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1074/mcp.RA118.000610", "sha256": "sha256:88a819bfea18edbf1886842ad56d141f88f53380b31477789568bf2c65fe92d8", "bytes": 1557, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1074/mcp.RA118.000610", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC5986252", "source": "ncbi_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}], "gaps": []}, "analysis": {"state": "absent", "methods": [], "targets": [], "gaps": ["method", "operations"]}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "blocked", "tier": "R4", "blocking_axis": "data", "blocked_on": "data:accession_absent", "axes": {"method": {"tier": "R4", "expressible": false, "required_operations": [], "missing_operations": [], "basis": "The reader quoted the method the paper names (not named), but the corpus's method extractor could not map it onto a DSL operation, so the method is published but not expressible."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R4", "reachable": false, "accessions": [], "resolved_accessions": [], "statements": [], "basis": "The paper names no accession to its source data, so the data has to come from the authors."}}, "can_run": {"dsl_operations": [], "assets": ["source:pmid:29572246"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:None"]}, "gaps": ["data:accession_absent"]}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:33:57Z", "independence": "single_reader"}, "evidence_check": {"method": null, "availability": null}, "calls": 2, "usage": {"prompt_tokens": 1614, "completion_tokens": 555, "cached_tokens": 528}}, "human_critique": null, "stages": [{"id": "extraction", "state": "complete", "reader": "MiniMax-M3.1-Flash", "provider": "minimax"}], "gaps": ["review.independent_reader", "review.machine_critique", "review.human_critique"]}, "execution": {"state": "absent", "status": "not_run", "mode": null, "runs": [], "gaps": ["execution.not_run"]}, "provenance": {"entities": [{"id": "pmid:29572246", "type": "paper", "label": "pmid:29572246"}, {"id": "source:pmid:29572246", "type": "manuscript", "label": "PMID 29572246 full text"}, {"id": "data:geo:None", "type": "dataset", "label": "GEO None"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:29572246", "type": "paper", "label": "pmid:29572246"}, {"id": "source:pmid:29572246", "type": "manuscript", "label": "PMID 29572246 full text"}, {"id": "data:geo:None", "type": "dataset", "label": "GEO None"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-29572246", "type": "extraction", "used": ["source:pmid:29572246"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-None", "type": "accession_resolution", "used": ["data:geo:None"], "agent": "agent:corpus-assay-engine"}], "agents": [{"id": "agent:corpus-assay-engine", "type": "software", "label": "Corpus assay engine"}, {"id": "agent:minimax-reader", "type": "software", "label": "MiniMax literature reader"}], "source_run_id": "reading-sci-2026-11-01", "dsl_catalogue_fingerprint": "343fb30756ba6ec3", "capability_table_fingerprint": "2cb3e42f047d2ecf", "snapshot_id": "ba34b49490d9bfaf"}, "lineage": {"parent_id": "pmid:29572246", "parent_hash": "sha256:b16966b473e6994980d5a39b7b0834c57df371bb2b1a57bb8245d867af4ce381", "fork_of": null, "generation": 1}, "gaps": ["execution.not_run", "method", "operations", "review.human_critique", "review.independent_reader", "review.machine_critique", "step:obtain_source_data blocked on data:accession_absent"], "assays": [{"role": "data_generation", "definition_id": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.77, "evidence": ["h/survival was tested by silencing them with siRNA. Knocking down USP11, CTTN, ACAA2, and EIF4H"], "order_basis": "paper_text_order:1179", "id": "assay:1"}]}