The Journal of Cell Biology, Vol 121, 643-654, Copyright © 1993 by The Rockefeller University Press

ARTICLES

Regulation of E-cadherin-mediated adhesion by muscarinic acetylcholine receptors in small cell lung carcinoma

CL Williams, VY Hayes, AM Hummel, JE Tarara and TJ Halsey
Department of Immunology, Mayo Clinic and Foundation, Rochester, Minnesota 55905.

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.
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