AUTHOR=Braadland Peder R., Ramberg Håkon A., Grytli Helene H., Taskén Kristin A.

TITLE=β-Adrenergic receptor signaling in prostate cancer

JOURNAL=Frontiers in Oncology

VOLUME=4

YEAR=2015

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2014.00375

DOI=10.3389/fonc.2014.00375

ISSN=2234-943X

ABSTRACT=<p>Enhanced sympathetic signaling, often associated with obesity and chronic stress, is increasingly acknowledged as a contributor to cancer aggressiveness. In prostate cancer, intact sympathetic nerves are critical for tumor formation, and sympathectomy induces apoptosis and blocks tumor growth. Perineural invasion, involving enrichment of intra-prostatic nerves, is frequently observed in prostate cancer and is associated with poor prognosis. β<sub>2</sub>-adrenergic receptor (ADRB2), the most abundant receptor for sympathetic signals in prostate luminal cells, has been shown to regulate trans-differentiation of cancer cells to neuroendocrine-like cells and to affect apoptosis, angiogenesis, epithelial–mesenchymal transition, migration, and metastasis. Epidemiologic studies have shown that use of β-blockers, inhibiting β-adrenergic receptor activity, is associated with reduced prostate cancer-specific mortality. In this review, we aim to present an overview on how β-adrenergic receptor and its downstream signaling cascade influence the development of aggressive prostate cancer, primarily through regulating neuroendocrine differentiation.</p>