Changes in the Acetylcholinesterase Enzymatic Activity in Tumor Development and Progression

SIMPLE SUMMARY: The cholinergic system’s participation in cancer development has been reviewed, highlighting the involvement of acetylcholine receptors (AChR) and acetylcholine (ACh). It has also been observed that acetylcholinesterase (AChE) plays a relevant role in cancer because AChE is an indirect regulator of AChRs by hydrolyzing ACh; however, controversy has been observed regarding the participation in cancer, since in some tumors the enzymatic activity increases, while in others the activity drops. This review focuses on analyzing the involvement of AChE during cancer progression and proposes AChE as a central regulator in the initiation and progression of cancer via the cholinergic system. Modulating ACh levels with AChE could regulate AChRs differentially, thus driving diverse cancer events. ABSTRACT: Acetylcholinesterase is a well-known protein because of the relevance of its enzymatic activity in the hydrolysis of acetylcholine in nerve transmission. In addition to the catalytic action, it exerts non-catalytic functions; one is associated with apoptosis, in which acetylcholinesterase could significantly impact the survival and aggressiveness observed in cancer. The participation of AChE as part of the apoptosome could explain the role in tumors, since a lower AChE content would increase cell survival due to poor apoptosome assembly. Likewise, the high Ach content caused by the reduction in enzymatic activity could induce cell survival mediated by the overactivation of acetylcholine receptors (AChR) that activate anti-apoptotic pathways. On the other hand, in tumors in which high enzymatic activity has been observed, AChE could be playing a different role in the aggressiveness of cancer; in this review, we propose that AChE could have a pro-inflammatory role, since the high enzyme content would cause a decrease in ACh, which has also been shown to have anti-inflammatory properties, as discussed in this review. In this review, we analyze the changes that the enzyme could display in different tumors and consider the different levels of regulation that the acetylcholinesterase undergoes in the control of epigenetic changes in the mRNA expression and changes in the enzymatic activity and its molecular forms. We focused on explaining the relationship between acetylcholinesterase expression and its activity in the biology of various tumors. We present up-to-date knowledge regarding this fascinating enzyme that is positioned as a remarkable target for cancer treatment.