Adrenomedullin blockade suppresses sunitinib-resistant renal cell carcinoma growth by targeting the ERK/MAPK pathway.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:27556517", "kind": "science-record", "revision": 7, "content_hash": "sha256:faa888068394b095ae2b953c76206c0fa1b32cc42bf856f70f44883a0529ddd4", "created_at": "2026-11-01T15:40:19Z", "updated_at": "2026-11-01T21:20:38Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Adrenomedullin blockade suppresses sunitinib-resistant renal cell carcinoma growth by targeting the ERK/MAPK pathway.", "doi": "10.18632/oncotarget.11463", "pmid": "27556517", "authors": ["Yongqian Gao", "Jinyi Li", "Na Qiao", "Qingsong Meng", "Ming Zhang", "Xin Wang", "Jianghua Jia", "Shuwen Yang", "Changbao Qu", "Wei Li", "Dongbin Wang"], "journal": "Oncotarget", "year": 2016, "abstract": "PURPOSE: To evaluate the mechanisms underlying sunitinib resistance in RCC and to identify targets that may be used to overcome this resistance.\nRESULTS: Reanalysis of transcriptome microarray datasets (GSE64052 and GSE76068) showed that adrenomedullin expression was increased in sunitinib-resistant tumors. And adrenomedullin expression was increased in sunitinib-resistant tumor xenografts, accompanied by upregulation of phospho-ERK levels. However, blocking adrenomedullin inhibited sunitinib-resistant tumor growth. Treatment of RCC cells with sunitinib and ADM22-52 was superior to monotherapy with either agent. Additionally, adrenomedullin upregulated cAMP and activated the ERK/MAPK pathway, promoting cell proliferation, while knockdown of adrenomedullin inhibited RCC cell growth and invasion in vitro.\nMATERIALS AND METHODS: We searched the Gene Expression Omnibus (GEO) database to find data regarding sunitinib-resistant RCC. These data were subsequently reanalyzed to identify targets that contribute to sunitinib resistance, and adrenomedullin upregulation was found to mediate sunitinib resistance in RCC. Then, we created an RCC mouse xenograft model. Mice were treated with sunitinib, an adrenomedullin receptor antagonist (ADM22-52), a MEK inhibitor (PD98059) and different combinations of these three drugs to investigate their effects on tumor growth. RCC cells (786-0) were cultured in vitro and treated with an ADM22-52 or PD98059 to determine whether adrenomedullin activates the ERK/MAPK pathway. Adrenomedullin was knocked down in 786-0 cells via siRNA, and the effects of this knockdown on cell were subsequently investigated.\nCONCLUSIONS: Adrenomedullin plays an important role in RCC resistance to sunitinib treatment. 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RESULTS: Reanalysis of transcriptome microarray datasets (GSE64052 and GSE76068) showed that", "database, identified the following 2 sets of microarray data regarding renal cell carcinoma resistan", "1). In 2015, Zhang L et al. published their microarray data analysis of 786-0 cell xenografts that"], "order_basis": "paper_text_order:255", "id": "assay:1"}, {"role": "data_generation", "definition_id": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["pathway, promoting cell proliferation, while knockdown of adrenomedullin inhibited RCC cell growth", "6-0 cells via siRNA, and the effects of this knockdown on cell were subsequently investigated. CONC", "medullin was knocked down in 786-0 cells via siRNA, and the effects of this knockdown on cell w"], "order_basis": "paper_text_order:811", "id": "assay:2"}, {"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["en, we created an RCC mouse xenograft model. Mice were treated with sunitinib, an adrenomedullin re", "b resistance in RCC. Then, we created an RCC mouse xenograft model. Mice were treated with suni", "eveloped. At the end of the experiments, the mice were sacrificed, and the tumors were collected. Subsequently", "ges in pretreated versus sunitinib-resistant murine 786-0 tumors. The columns represent the samp"], "order_basis": "paper_text_order:1221", "id": "assay:3"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.77, "evidence": ["ects on tumor growth. RCC cells (786-0) were cultured in vitro and treated with an ADM22-52 or PD9805"], "order_basis": "paper_text_order:1471", "id": "assay:4"}]}