{"id":"e5e36248-30dc-5788-afd4-6704385e9486","stable_key":"2921131d-0ba0-51d3-8f59-8c4be3b9ac08:cucurbitacin-i-jak-stat-knockdown","predicate":"when_silenced_does_not_reproduce","statement":"Silencing STAT3 or JAK2 did not reproduce cucurbitacin I-mediated Rac1 inhibition in the tested human breast-cancer cells.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"neutral","is_public":true,"mechanism_event_id":"5e020d49-b550-5026-a50e-0ad6685117c2","mechanism_event_label":"Removing the familiar signaling pathway did not explain this movement effect.","subject":{"id":"dc129d3d-aaa0-5511-9a60-3e3880b0eb0f","slug":"stat3","display_name":"STAT3","entity_type_key":"protein"},"object":{"id":"8a96d7c7-d28d-5615-94a7-3c397bed8f9d","slug":"rac1","display_name":"RAC1","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"5e020d49-b550-5026-a50e-0ad6685117c2","stable_key":"2921131d-0ba0-51d3-8f59-8c4be3b9ac08:cucurbitacin-i-jak-stat-knockdown-event","event_type":"observed_relationship","label":"Removing the familiar signaling pathway did not explain this movement effect.","description":"Silencing STAT3 or JAK2 did not reproduce cucurbitacin I-mediated Rac1 inhibition in the tested human breast-cancer cells.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"dc129d3d-aaa0-5511-9a60-3e3880b0eb0f","slug":"stat3","display_name":"STAT3","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"8a96d7c7-d28d-5615-94a7-3c397bed8f9d","slug":"rac1","display_name":"RAC1","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"5f9b52fd-ebca-5dfb-b959-c5d4aa1ab70f","slug":"human-jak2","display_name":"Human Janus kinase 2 / JAK2","entity_type_key":"protein"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"55ef0ba6-495d-5cc4-88c5-0772ab25d0fe","slug":"cucurbitacin-i","display_name":"Cucurbitacin I","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"evidence_access","value_text":"Primary abstract","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"RNA interference in human breast-cancer cells.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Negative pathway test is limited to these endpoints and cells; it does not show that all JAK/STAT effects are absent.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Cucurbitacins collection; species, compartment, exposure, co-substrates and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"cucurbitacin","display_name":"Cucurbitacins","entity_type_key":"chemical_species"}},{"dimension":"plain_language","value_text":"Removing the familiar signaling pathway did not explain this movement effect.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Cucurbitacin I inhibits Rac1 activation in breast cancer cells by a reactive oxygen species-mediated mechanism and independently of Janus tyrosine kinase 2 and P-Rex1. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23478800/ · DOI 10.1124/mol.112.084293","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"4e0507ba-abdf-511a-89b5-9f3f3f66fe0e","evidence_kind":"source_excerpt","locator":"Lines 172-178","start_line":172,"end_line":178,"excerpt":"## cucurbitacin-i-jak-stat-knockdown\nRemoving the familiar signaling pathway did not explain this movement effect.\nSilencing STAT3 or JAK2 did not reproduce cucurbitacin I-mediated Rac1 inhibition in the tested human breast-cancer cells.\nModel: RNA interference in human breast-cancer cells.\nLimitations: Negative pathway test is limited to these endpoints and cells; it does not show that all JAK/STAT effects are absent.\nEvidence access: Primary abstract\nCucurbitacin I inhibits Rac1 activation in breast cancer cells by a reactive oxygen species-mediated mechanism and independently of Janus tyrosine kinase 2 and P-Rex1. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23478800/ · DOI 10.1124/mol.112.084293","model_system":"RNA interference in human breast-cancer cells.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Original curation paraphrase; evidence access and experimental limitations specified.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"77324310-00ce-5d28-9fc7-595fddae86b9","stable_key":"import-2921131d-0ba0-51d3-8f59-8c4be3b9ac08","title":"Cucurbitacins: thiol chemistry, cytoskeleton, metabolic dependencies and signaling (2026-09-20)","document_type":"imported_text","citation_label":"AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text.","file_path":"","sha256":"5c23ec61b9cf3d2966fb081d8617e1e1f7c522e86419b8ba2dcae09590121123","revision_id":"74251a06-3ba5-506c-b428-700eca0fb432","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}