biostudies-literatureBhat RDepartment of Defense BCRPBreast Cancer Research FoundationNCI NIH HHSNIHNIH HHS1972https://www.ebi.ac.uk/biostudies/studies/S-EPMC8817007biostudies-literatureUnknown12(1)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 Scientific reportsNPY1R exerts inhibitory action on estradiol-stimulated growth and predicts endocrine sensitivity and better survival in ER-positive breast cancer.PMC8817007W81XWH-14-1-0341CA125123W81XWH-14-1-0340BCRF-18-145P50 CA186784CA186784-01P50 CA058183BCRF-19-145Nanda STrivedi MVVasaikar SFu XDe Angelis CAbdulkareem NMCataldo MLSchiff RBhat RThangavel HBae LZhang BfalseNPY1R exerts inhibitory action on estradiol-stimulated growth and predicts endocrine sensitivity and better survival in ER-positive breast cancer.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 2022-01-01T00:00:00Z2022 Feb2026-05-30T15:13:02.493Z2025-04-19T22:37:42.827ZS-EPMC88170073512178210.1038/s41598-022-05949-7