Acetylcholinesterase and human cancers.

Abstract

The enzyme acetylcholinesterase (AChE) is a serine hydrolase whose primary function is to degrade acetylcholine (ACh) and terminate neurotransmission. Apart from its role in synaptic transmission, AChE has several "non-classical" functions in non-neuronal cells. AChE is involved in cellular growth, apoptosis, drug resistance pathways, response to stress signals and inflammation. The observation that the functional activity of AChE is altered in human tumors (relative to adjacent matched normal tissue) has raised several intriguing questions about its role in the pathophysiology of human cancers. Published reports show that AChE is a vital regulator of oncogenic signaling pathways involving proliferation, differentiation, cell-cell adhesion, migration, invasion and metastasis of primary tumors. The objective of this book chapter is to provide a comprehensive overview of the contributions of the AChE-signaling pathway in the growth of progression of human cancers. The AChE isoforms, AChE-T, AChE-R and AChE-S are robustly expressed in human cancer cell lines as well in human tumors (isolated from patients). Traditionally, AChE-modulators have been used in the clinic for treatment of neurodegenerative disorders. Emerging studies reveal that these drugs could be repurposed for the treatment of human cancers. The discovery of potent, selective AChE ligands will provide new knowledge about AChE-regulatory pathways in human cancers and foster the hope of novel therapies for this disease.