?-Adrenergic Receptor Signaling in Prostate Cancer.

ABSTRACT: 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. ?2-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 ?-blockers, inhibiting ?-adrenergic receptor activity, is associated with reduced prostate cancer-specific mortality. In this review, we aim to present an overview on how ?-adrenergic receptor and its downstream signaling cascade influence the development of aggressive prostate cancer, primarily through regulating neuroendocrine differentiation.

SUBMITTER: Braadland PR 

PROVIDER: S-EPMC4290544 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature