Role of α- and β-adrenergic signaling in phenotypic targeting: significance in benign and malignant urologic disease
| Autor: | T. Ganta, Peter Wiklund, Natasha Kyprianou, Ash Tewari, Dara Lundon, S. Gaglani, Meredith Mihalopoulos, Maddison Archer, Reza Mehrazin, H.-S. Jang, L. Björnebo, Steven A. Kaplan, Navneet Dogra, K. Tsao, Babu J. Padanilam, Mi Ra Noh, Zachary Dovey, F. Lucien, Anna Lantz, Mantu Gupta, Jennifer A. Stockert, Nihal Mohamed, Ketan K. Badani, Johnathan A. Khusid, A. Zahalka |
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| Rok vydání: | 2021 |
| Předmět: |
Male
Urologic Diseases 0301 basic medicine Urologic Neoplasms Epithelial-Mesenchymal Transition Angiogenesis Urinary system Adrenergic beta-Antagonists Urologic tumors Review Adrenoceptors Biochemistry 03 medical and health sciences 0302 clinical medicine Receptors Adrenergic alpha-1 Tumor Microenvironment medicine Humans Urinary Tract Molecular Biology Tumor microenvironment QH573-671 Genitourinary system business.industry Prostate Cancer Cell Biology Kidney disease medicine.disease Fibrosis Autonomic nervous system 030104 developmental biology α- and β-adrenergic blockade 030220 oncology & carcinogenesis Cell polarity Cancer research Medicine Urologic disease Receptors Adrenergic beta-1 Signal transduction Cytology business Phenotypic landscape Signal Transduction |
| Zdroj: | Cell Communication and Signaling, Vol 19, Iss 1, Pp 1-21 (2021) Cell Communication and Signaling : CCS |
| ISSN: | 1478-811X |
| DOI: | 10.1186/s12964-021-00755-6 |
| Popis: | The urinary tract is highly innervated by autonomic nerves which are essential in urinary tract development, the production of growth factors, and the control of homeostasis. These neural signals may become dysregulated in several genitourinary (GU) disease states, both benign and malignant. Accordingly, the autonomic nervous system is a therapeutic target for several genitourinary pathologies including cancer, voiding dysfunction, and obstructing nephrolithiasis. Adrenergic receptors (adrenoceptors) are G-Protein coupled-receptors that are distributed throughout the body. The major function of α1-adrenoceptors is signaling smooth muscle contractions through GPCR and intracellular calcium influx. Pharmacologic intervention of α-and β-adrenoceptors is routinely and successfully implemented in the treatment of benign urologic illnesses, through the use of α-adrenoceptor antagonists. Furthermore, cell-based evidence recently established the antitumor effect of α1-adrenoceptor antagonists in prostate, bladder and renal tumors by reducing neovascularity and impairing growth within the tumor microenvironment via regulation of the phenotypic epithelial-mesenchymal transition (EMT). There has been a significant focus on repurposing the routinely used, Food and Drug Administration-approved α1-adrenoceptor antagonists to inhibit GU tumor growth and angiogenesis in patients with advanced prostate, bladder, and renal cancer. In this review we discuss the current evidence on (a) the signaling events of the autonomic nervous system mediated by its cognate α- and β-adrenoceptors in regulating the phenotypic landscape (EMT) of genitourinary organs; and (b) the therapeutic significance of targeting this signaling pathway in benign and malignant urologic disease. Video abstract Supplementary Information The online version contains supplementary material available at 10.1186/s12964-021-00755-6. |
| Databáze: | OpenAIRE |
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