{"id":"ab992ed2-6aa8-5b1f-8312-63f4dcdcb43c","stable_key":"e37461ea-ea5d-5e2c-8091-138305f6dd70:l-aspartate-hypoxia-hif-ca9","predicate":"promotes_ca9_dependent_scavenging","statement":"Genetic and pharmacological experiments linked hypoxia-enhanced macropinocytosis to HIF1A and its target CA9 in KRAS-mutant PDAC models.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"60751738-4fb6-526d-9ccb-ecb40d4fcc78","mechanism_event_label":"An oxygen-response program increased an alternative nutrient-acquisition route.","subject":{"id":"22b3e241-94b0-55fd-a233-c63af92520d8","slug":"hif1a","display_name":"HIF-1 alpha","entity_type_key":"protein"},"object":{"id":"e619a420-21e3-5341-b54c-9da535c00549","slug":"human-pdac-macropinocytosis","display_name":"Macropinocytic protein scavenging by human PDAC cells","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"60751738-4fb6-526d-9ccb-ecb40d4fcc78","stable_key":"e37461ea-ea5d-5e2c-8091-138305f6dd70:l-aspartate-hypoxia-hif-ca9-event","event_type":"observed_relationship","label":"An oxygen-response program increased an alternative nutrient-acquisition route.","description":"Genetic and pharmacological experiments linked hypoxia-enhanced macropinocytosis to HIF1A and its target CA9 in KRAS-mutant PDAC models.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"22b3e241-94b0-55fd-a233-c63af92520d8","slug":"hif1a","display_name":"HIF-1 alpha","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"e619a420-21e3-5341-b54c-9da535c00549","slug":"human-pdac-macropinocytosis","display_name":"Macropinocytic protein scavenging by human PDAC cells","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"0a0923d3-72b7-5d6a-bf3a-5a7a3071a09b","slug":"l-aspartate","display_name":"L-Aspartate","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"9f95f91a-4b6a-5bcf-bcb8-82444cc8a344","slug":"ca9","display_name":"Human carbonic anhydrase IX / CA9","entity_type_key":"protein"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary full text","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human and mouse PDAC model program; human-cell HIF1A/CA9 manipulations.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"CA9 is a mediator in the tested models, not a universal aspartate transporter.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"L-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"l-aspartate","display_name":"L-Aspartate","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"An oxygen-response program increased an alternative nutrient-acquisition route.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Adaptive stimulation of macropinocytosis overcomes aspartate limitation in cancer cells under hypoxia. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35726024/ · DOI 10.1038/s42255-022-00583-z","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"117af7c6-b35a-5ae4-aa02-054092c8bcd9","evidence_kind":"source_excerpt","locator":"Lines 266-272","start_line":266,"end_line":272,"excerpt":"## l-aspartate-hypoxia-hif-ca9\nAn oxygen-response program increased an alternative nutrient-acquisition route.\nGenetic and pharmacological experiments linked hypoxia-enhanced macropinocytosis to HIF1A and its target CA9 in KRAS-mutant PDAC models.\nModel: Human and mouse PDAC model program; 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