Neuroendocrine influences on cancer progression

Abstract

During the past decade, new studies have continued to shed light on the role of neuroendocrine regulation of downstream physiological and biological pathways relevant to cancer growth and progression. More specifically, our knowledge of the effects of the sympathetic nervous system (SNS) on cancer biology has been greatly expanded by new data demonstrating how the cellular immune response, inflammatory processes, tumor-associated angiogenesis, and tumor cell invasion and survival converge to promote tumor growth. This review will summarize these studies, while synthesizing clinical, cellular and molecular research that has continued to unearth the biological events mediating the interplay between SNS-related processes and cancer progression.

Figure 1. Overview of catecholamine-mediated signaling pathways in cancer

Norepinephrine (NE) or Epinephrine (Epi) bind to beta adrenergic receptors (ADRB), resulting in increased cyclic AMP (cAMP) levels that induce Protein Kinase A (PKA) activity. PKA can then phosphorylate several proteins, such as CREB/ATF, GATA1 and Src leading to increased activity of several pro-tumoral proteins. Additionally, elevated levels of cAMP also result in the activation of Exchange Protein Activated by cAMP (EPAC) and its associated signaling cascade. Conversely, upon binding to dopamine receptor 2 (DR2), Dopamine (DA) can inhibit Adenylyl cyclase (AC) function leading to decreased cAMP and downstream pro-tumoral protein levels.