{"doi":"10.1038/s41598-022-05949-7","title":"NPY1R exerts inhibitory action on estradiol-stimulated growth and predicts endocrine sensitivity and better survival in ER-positive breast cancer","abstract":"G Protein-Coupled Receptors (GPCRs) represent the largest superfamily of cell-surface proteins. However, the expression and function of majority of GPCRs remain unexplored in breast cancer (BC). We interrogated the expression and phosphorylation status of 398 non-sensory GPCRs using the landmark BC proteogenomics and phosphoproteomic dataset from The Cancer Genome Atlas. Neuropeptide Y Receptor Y1 (NPY1R) gene and protein expression were significantly higher in Luminal A tumors versus other BC subtypes. The trend of NPY1R gene, protein, and phosphosite (NPY1R-S368s) expression was decreasing in the order of Luminal A, Luminal B, Basal, and human epidermal growth factor receptor 2 (HER2) subtypes. NPY1R gene expression increased in response to estrogen and reduced with endocrine therapy in estrogen receptor-positive (ER+) BC cells and xenograft models. Conversely, NPY1R expression decreased in ER+ BC cells resistant to endocrine therapies (estrogen deprivation, tamoxifen, and fulvestrant) in vitro and in vivo. NPY treatment reduced estradiol-stimulated cell growth, which was reversed by NPY1R antagonist (BIBP-3226) in ER+ BC cells. Higher NPY1R gene expression predicted better relapse-free survival and overall survival in ER+ BC. Our study demonstrates that NPY1R mediates the inhibitory action of NPY on estradiol-stimulated growth of ER+ BC cells, and its expression serves as a biomarker to predict endocrine sensitivity and survival in ER+ BC patients.","journal":"Scientific Reports","year":2022,"id":244673,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":27,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8812,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":708903,"name":"Hariprasad Thangavel","orcid":"0000-0001-5119-2661","position":1,"is_corresponding":false},{"id":708901,"name":"Noor Mazin Abdulkareem","orcid":"0000-0003-0189-3069","position":2,"is_corresponding":false},{"id":108202,"name":"Suhas Vasaikar","orcid":"0000-0001-9763-3899","position":3,"is_corresponding":false},{"id":263245,"name":"Carmine De Angelis","orcid":"0000-0003-1158-4630","position":4,"is_corresponding":false},{"id":879091,"name":"Leon Bae","orcid":null,"position":5,"is_corresponding":false},{"id":639738,"name":"Maria Letizia Cataldo","orcid":null,"position":6,"is_corresponding":false},{"id":639740,"name":"Sarmistha Nanda","orcid":null,"position":7,"is_corresponding":false},{"id":263244,"name":"Xiaoyong Fu","orcid":"0000-0003-0005-6496","position":8,"is_corresponding":false},{"id":7638,"name":"Bing Zhang","orcid":"0000-0001-8676-2425","position":9,"is_corresponding":false},{"id":263252,"name":"Rachel Schiff","orcid":"0000-0003-1696-5213","position":10,"is_corresponding":false},{"id":708904,"name":"Meghana V. Trivedi","orcid":"0000-0002-0585-5580","position":11,"is_corresponding":false},{"id":708902,"name":"Raksha R. Bhat","orcid":"0000-0002-0026-1118","position":0,"is_corresponding":true}],"reference_count":78,"raw_metadata":null,"created_at":"2026-07-19T00:23:30.364338Z","pmid":"35121782","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}