Acetylcholinesterase (AChE) is well established as having non-
cholinergic functions and is also expressed in breast tumours where its function(s) is not known. Recently, a candidate
peptide sequence towards the C-terminal of the AChE molecule has been identified, as the salient site remote from normal catalysis in neurons, and possibly other cells. The main aim of this study was to explore the possibility that '
AChE-peptide' might also affect human
breast cancer cells. Uptake of the non-cytotoxic tracer
horseradish peroxidase (HRP) was used as an index of endocytosis, a key component of the metastatic cascade, representing exocytosis/secretory membrane activity and/or plasma membrane
protein turnover.
AChE-peptide had no affect on the weakly metastatic MCF-7 human
breast cancer cell line. By contrast, application of
AChE-peptide to the strongly metastatic MDA-MB-231 cells resulted in a dose-dependent inhibition of HRP uptake; treatment with a scrambled variant of the
peptide of comparable
amino acid length was ineffective. The action of
AChE-peptide was suppressed by lowering the extracellular Ca2+ concentration and co-applying a selective antagonist of alpha7, but not alpha4/beta2,
nicotinic receptor. The results suggest that
AChE-peptide has a novel, selective bioactivity on
breast cancer cells and can potentiate metastatic cell behaviour.