NPY1R exerts inhibitory action on estradiol-stimulated growth and predicts endocrine sensitivity and better survival in ER-positive breast cancer
| Autor: | Raksha Bhat, Hariprasad Thangavel, Noor Mazin Abdulkareem, Suhas Vasaikar, Carmine De Angelis, Leon Bae, Maria Letizia Cataldo, Sarmistha Nanda, Xiaoyong Fu, Bing Zhang, Rachel Schiff, Meghana V. Trivedi |
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| Přispěvatelé: | Bhat, R., Thangavel, H., Abdulkareem, N. M., Vasaikar, S., De Angelis, C., Bae, L., Cataldo, M. L., Nanda, S., Fu, X., Zhang, B., Schiff, R., Trivedi, M. V. |
| Rok vydání: | 2022 |
| Předmět: |
Antineoplastic Agents
Hormonal Receptor ErbB-2 Science Breast Neoplasms Receptors G-Protein-Coupled Mice Cell Line Tumor Endocrine Gland Neoplasms Animals Humans Fulvestrant Cell Proliferation Multidisciplinary Estradiol Animal Endocrine Gland Neoplasm Estrogen Receptor alpha Estrogens Estrogen Receptors Neuropeptide Y Gene Expression Regulation Neoplastic Tamoxifen Drug Resistance Neoplasm Medicine Heterografts Female Neoplasm Recurrence Local Heterograft Breast Neoplasm Human |
| Zdroj: | Scientific Reports, Vol 12, Iss 1, Pp 1-12 (2022) |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-022-05949-7 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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