Upregulation of adenylate cyclase 3 (ADCY3) increases the tumorigenic potential of cells by activating the CREB pathway.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:24113161", "kind": "science-record", "revision": 8, "content_hash": "sha256:708be96b2ab64b0ed8230699ebaf2f2f1673f8be0cc52096fb391cc20c528b67", "created_at": "2026-11-01T15:40:03Z", "updated_at": "2026-11-01T21:58:13Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Upregulation of adenylate cyclase 3 (ADCY3) increases the tumorigenic potential of cells by activating the CREB pathway.", "doi": "10.18632/oncotarget.1324", "pmid": "24113161", "authors": ["Seung-Hyun Hong", "Sung-Ho Goh", "Sang Jin Lee", "Jung-Ah Hwang", "Jieun Lee", "Il-Ju Choi", "Hyehyun Seo", "Jong-Hoon Park", "Hiromu Suzuki", "Eiichiro Yamamoto", "In-Hoo Kim", "Jin Sook Jeong", "Mi Ha Ju", "Dong-Hee Lee", "Yeon-Su Lee"], "journal": "Oncotarget", "year": 2013, "abstract": "Adenylate cyclase 3 (ADCY3) is a widely expressed membrane-associated protein in human tissues, which catalyzes the formation of cyclic adenosine-3',5'-monophosphate (cAMP). However, our transcriptome analysis of gastric cancer tissue samples (NCBI GEO GSE30727) revealed that ADCY3 expression was specifically altered in cancer samples. Here we investigated the tumor-promoting effects of ADCY3 overexpression and confirmed a significant correlation between the upregulation of ADCY3 and Lauren's intestinal-type gastric cancers. ADCY3 overexpression increased cell migration, invasion, proliferation, and clonogenicity in HEK293 cells; conversely, silencing ADCY3 expression in SNU-216 cells reduced these phenotypes. Interestingly, ADCY3 overexpression increased both the mRNA level and activity of matrix metalloproteinase 2 (MMP2) and MMP9 by increasing the levels of cAMP and phosphorylated cAMP-responsive element-binding protein (CREB). Consistent with these findings, treatment with a protein kinase A (PKA) inhibitor decreased MMP2 and MMP9 expression levels in ADCY3-overexpressing cells. Knockdown of ADCY3 expression by stable shRNA in human gastric cancer cells suppressed tumor growth in a tumor xenograft model. Thus, ADCY3 overexpression may exert its tumor-promoting effects via the cAMP/PKA/CREB pathway. Additionally, bisulfite sequencing of the ADCY3 promoter region revealed that gene expression was reduced by hypermethylation of CpG sites, and increased by 5-Aza-2'-deoxycytidine (5-Aza-dC)-induced demethylation. Our study is the first to report an association of ADCY3 with gastric cancer as well as its tumorigenic potentials. In addition, we demonstrate that the expression of ADCY3 is regulated through an epigenetic mechanism. Further study on the mechanism of ADCY3 in tumorigenesis will provide the basis as a new molecular target of gastric cancer.", "claims": [{"id": "claim-method", "statement": "The statistical significance of differences between groups was determined using Student's t-test.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:24113161", "locator": "sections[19] \"Statistical analysis\" paragraph 2", "quote": "The statistical significance of differences between groups was determined using Student's t-test."}], "state": "complete"}, {"id": "claim-data-access", "statement": "We performed microarray analyses to compare gene expression profiles of human gastric cancer samples and adjacent normal tissue (NCBI GEO accession no.: GSE30727) [9].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:24113161", "locator": "sections[1] \"INTRODUCTION\" paragraph 3", "quote": "We performed microarray analyses to compare gene expression profiles of human gastric cancer samples and adjacent normal tissue (NCBI GEO accession no.: GSE30727) [9]."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The paper used Student's t-test, with P-values below 0.05 considered statistically significant, and obtained microarray source data from NCBI GEO accession GSE30727; its headline result was that “ADCY3 overexpression may exert its tumor-promoting effects via the cAMP/PKA/CREB pathway.”", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:24113161", "locator": "sections[19] \"Statistical analysis\" paragraph 2", "quote": "The statistical significance of differences between groups was determined using Student's t-test. P-values less than 0.05 were considered statistically significant."}, {"asset": "source:pmid:24113161", "locator": "sections[1] \"INTRODUCTION\" paragraph 3", "quote": "We performed microarray analyses to compare gene expression profiles of human gastric cancer samples and adjacent normal tissue (NCBI GEO accession no.: GSE30727) [9]."}, {"asset": "source:pmid:24113161", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Thus, ADCY3 overexpression may exert its tumor-promoting effects via the cAMP/PKA/CREB pathway."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "The paper used Student's t-test, with P-values below 0.05 considered statistically significant, and obtained microarray source data from NCBI GEO accession GSE30727; its headline result was that “ADCY3 overexpression may exert its tumor-promoting effects via the cAMP/PKA/CREB pathway.”", "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:24113161"], "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": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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Cells were cultured in appropriate growth media (Corning Cellgro, M", "k, Seoul, Korea); AGS, KATO III, MKN28, H23, A549, HCT-116, SNU-81, SK-BR-3, JIMT-1, U2OS, and", "H23, A549, HCT-116, SNU-81, SK-BR-3, JIMT-1, U2OS, and U87 (ATCC, Manassas, VA, USA); human de"], "order_basis": "paper_text_order:700", "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": ["ession levels in ADCY3-overexpressing cells. Knockdown of ADCY3 expression by stable shRNA in human", "lls. Knockdown of ADCY3 expression by stable shRNA in human gastric cancer cells suppressed tum"], "order_basis": "paper_text_order:1176", "id": "assay:2"}, {"role": "data_generation", "definition_id": "methylation_array", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["via the cAMP/PKA/CREB pathway. Additionally, bisulfite sequencing of the ADCY3 promoter region reve", "tatus of the ADCY3 promoter, genomic DNA was bisulfite-treated using the EZ DNA Methylation-Gold Ki", "assay (MS-HRM) was performed using 10 ng of bisulfite-treated genomic DNA and ResoLight dye in a L", "ed using Gene Scanning software (Roche). 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