Role of α- and β-adrenergic signaling in phenotypic targeting: significance in benign and malignant urologic disease

Cell Communication and Signaling

L. Björnebo¹  A. Lantz²  N. Dogra³  S. A. Kaplan⁴  H.-S. Jang⁴  J. A. Stockert⁴  A. Zahalka⁴  Z. Dovey⁴  J. A. Khusid⁴  M. Gupta⁴  B. Padanilam⁴  M. Archer⁴  M. R. Noh⁴  S. Gaglani⁴  N. Kyprianou⁵  K. K. Badani⁶  D. J. Lundon⁶  N. Mohamed⁶  A. K. Tewari⁶  R. Mehrazin⁶  P. Wiklund⁶  M. Mihalopoulos⁶  F. Lucien⁷  T. Ganta⁸  K. Tsao⁸ 

[1] Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden;Department of Molecular Medicine and Surgery, Section of Urology, Karolinska Institute, Stockholm, Sweden;Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden;Department of Pathology and Molecular and Cell Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA;Department of Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA;Department of Urology, Icahn School of Medicine at Mount Sinai, 6th Floor, 1425 Madison Avenue, 10029, New York, NY, USA;Department of Urology, Icahn School of Medicine at Mount Sinai, 6th Floor, 1425 Madison Avenue, 10029, New York, NY, USA;Department of Pathology and Molecular and Cell Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA;Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA;Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA;Department of Urology, Icahn School of Medicine at Mount Sinai, 6th Floor, 1425 Madison Avenue, 10029, New York, NY, USA;Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA;Department of Urology, Mayo Clinic, Rochester, MN, USA;Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA;Division of Hematology and Medical Oncology, Mount Sinai Hospital, New York, NY, USA;

关键词: Adrenoceptors;    α- and β-adrenergic blockade;    Urologic tumors;    Cell polarity;    Phenotypic landscape;    Fibrosis;    Kidney disease;   

DOI  :  10.1186/s12964-021-00755-6

来源: Springer

【 摘 要 】

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.C9YjncUJpTn6LEQXnrYmcfVideo abstract

【 授权许可】

CC BY