NPY1R exerts inhibitory action on estradiol-stimulated growth and predicts endocrine sensitivity and better survival in ER-positive breast cancer.
NPY1R exerts inhibitory action on estradiol-stimulated growth and predicts endocrine sensitivity and better survival in ER-positive breast cancer.
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DOI：
10.1038/s41598-022-05949-7
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发表时间：
2022-02-04
影响因子：
4.6
通讯作者：
Trivedi MV
中科院分区：
文献类型：
--
作者：
Bhat R;Thangavel H;Abdulkareem NM;Vasaikar S;De Angelis C;Bae L;Cataldo ML;Nanda S;Fu X;Zhang B;Schiff R;Trivedi MV
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.
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DOI：
10.1158/1078-0432.ccr-19-4191
发表时间：
2021-09-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
De Angelis C;Fu X;Cataldo ML;Nardone A;Pereira R;Veeraraghavan J;Nanda S;Qin L;Sethunath V;Wang T;Hilsenbeck SG;Benelli M;Migliaccio I;Guarducci C;Malorni L;Litchfield LM;Liu J;Donaldson J;Selenica P;Brown DN;Weigelt B;Reis-Filho JS;Park BH;Hurvitz SA;Slamon DJ;Rimawi MF;Jansen VM;Jeselsohn R;Osborne CK;Schiff R
通讯作者：
Schiff R
影响因子：
45.3
作者：
CLARK, GM;OSBORNE, CK;MCGUIRE, WL
通讯作者：
MCGUIRE, WL
影响因子：
3.9
作者：
Giuliano, Mario;Schiff, Rachel;Trivedi, Meghana V.
通讯作者：
Trivedi, Meghana V.
影响因子：
3.6
作者：
Colmers, William F.;El Bahh, Bouchaib
通讯作者：
El Bahh, Bouchaib
影响因子：
64.5
作者：
Ciriello G;Gatza ML;Beck AH;Wilkerson MD;Rhie SK;Pastore A;Zhang H;McLellan M;Yau C;Kandoth C;Bowlby R;Shen H;Hayat S;Fieldhouse R;Lester SC;Tse GM;Factor RE;Collins LC;Allison KH;Chen YY;Jensen K;Johnson NB;Oesterreich S;Mills GB;Cherniack AD;Robertson G;Benz C;Sander C;Laird PW;Hoadley KA;King TA;TCGA Research Network;Perou CM
通讯作者：
Perou CM