An acetylcholinesterase-derived peptide inhibits endocytic membrane activity in a human metastatic breast cancer cell line.
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.
Neuroscience Solutions to Cancer Research Group, Division of Cell and Molecular Biology, Sir Alexander Fleming Building, Imperial College London, South Kensington Campus, London SW7 2AZ, UK.
Pinar U
PU
Onganer
Mustafa B A
MB
Djamgoz
Kathryn
K
Whyte
Susan A
SA
Greenfield
D000110:Acetylcholinesterase / Q000502:physiology*; D001943:Breast Neoplasms / Q000473:pathology*; D002118:Calcium / Q000494:pharmacology; D045744:Cell Line, Tumor; D004079:Dihydro-beta-Erythroidine / Q000494:pharmacology; D004705:Endocytosis / Q000502:physiology; D005260:Female; D006735:Horseradish Peroxidase / Q000378:metabolism; D006801:Humans; D009362:Neoplasm Metastasis; D010446:Peptide Fragments / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000187:drug effects
D010446:Peptide Fragments; D011978:Receptors, Nicotinic; D004079:Dihydro-beta-Erythroidine; D006735:Horseradish Peroxidase; D000110:Acetylcholinesterase; D002118:Calcium