Regulation of E-cadherin-mediated adhesion by muscarinic acetylcholine receptors in small cell lung carcinoma.
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.
Department of Immunology, Mayo Clinic and Foundation, Rochester, Minnesota 55905.
C L
CL
Williams
V Y
VY
Hayes
A M
AM
Hummel
J E
JE
Tarara
T J
TJ
Halsey
D015820:Cadherins / Q000378:metabolism*; D018288:Carcinoma, Small Cell / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects; D002449:Cell Aggregation / Q000187:drug effects; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D009362:Neoplasm Metastasis; D010703:Phorbol Esters / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000378:metabolism / Q000502:physiology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D015820:Cadherins; D010703:Phorbol Esters; D011976:Receptors, Muscarinic; D011493:Protein Kinase C; D019204:GTP-Binding Proteins