Acetylcholine receptors: Key players in cancer development

Acetylcholine (ACh) was first identified as a classic neuromodulator and transmit signals through two subgroups of receptors, namely muscarinic receptors (mAChRs) and nicotinic receptors (nAChRs). Apart from its well-established physiological role in central nervous system (CNS) and peripheral nervous system (PNS), autonomic nervous system and neuromuscular junction, the widely distributed expression of AChRs in different human organs suggests roles in other biological processes in addition to synaptic transmission. Accumulating evidence revealed that cancer cell processes such as proliferation, apoptosis, angiogenesis and even epithelial-mesenchymal transition (EMT) are mediated by overexpression of AChRs in different kinds of tumors. In breast cancer, a7-nAChR and a9-nAChR were reported to be oncogenic. On the other hand, research on the role of mAChRs in breast cancer tumorgenesis is limited and confined to M3 receptor only. Since AChRs distributed in both CNS and PNS even non-neuronal tissues, there is an urgent need for the development of subtype-specific AChR antagonist which inhibits cancer cell progression with minimal intervention on the normal acetylcholine-regulated system within human body.