Regulation of E-Cadherin-Mediated Adhesion by Muscarinic Acetylcholine Receptors in Small Cell Lung Carcinoma

• Published in: The Journal of cell biology Vol. 121; no. 3; pp. 643 - 654
• Main Authors: Williams, Carol L., Hayes, Valerie Y., Hummel, Amber M., Tarara, James E., Halsey, Teresa J.
• Format: Journal Article
• Language: English
• Published: New York, NY Rockefeller University Press 01.05.1993; The Rockefeller University Press
• Subjects: Aggregation; Antibodies; Biochemistry; Biological and medical sciences; Cadherins; Cadherins - metabolism; Carcinoma, Small Cell - metabolism; Cell adhesion; Cell Adhesion - drug effects; Cell adhesion molecules; Cell Aggregation - drug effects; Cell interactions, adhesion; Cell lines; Cells; Cellular biology; Fundamental and applied biological sciences. Psychology; GTP-Binding Proteins - metabolism; Humans; Lung cancer; Lung Neoplasms - metabolism; Molecular and cellular biology; Molecules; Neoplasm Metastasis; Neural cell adhesion molecules; Phorbol Esters - pharmacology; Protein Kinase C - metabolism; Proteins; Receptors, Muscarinic - metabolism; Receptors, Muscarinic - physiology; Small cell lung carcinoma; Tumor Cells, Cultured - drug effects; Proteins; Cholinergic receptor; Regulation(control); Cell line; Cell cell interaction; Muscarinic receptor; Adhesion
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/jcb.121.3.643

We present the first evidence that adhesion mediated by a member of the cadherin gene family can be regulated by a G protein-coupled receptor. We show that activating the M3 muscarinic acetylcholine receptor (mAChR) rapidly induces E-cadherin-mediated adhesion in a small cell lung carcinoma (SCLC) cell line. This response is inhibited by E-cadherin antibodies, and does not occur in another SCLC cell line which expresses functional mAChR but reduced levels of E-cadherin. Protein kinase C may be involved, since phorbol 12-myristate 13-acetate also induces E-cadherin-mediated aggregation. Immunofluorescence analyses indicate that mAChR activation does not grossly alter E-cadherin surface expression or localization at areas of cell-cell contact, suggesting mAChR activation may increase E-cadherin binding activity. Our findings suggest that G protein-coupled receptors may regulate processes involving cadherin-mediated adhesion, such as embryonic development, neurogenesis, and cancer metastasis.