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Regulation of Cadherin-mediated Adhesion by the Small GTP-binding Protein Rho in Small Cell Lung Carcinoma Cells¹

Laboratory of Molecular Pharmacology, Guthrie Research Institute, Sayre, Pennsylvania 18840

Metastasis is one of the most important factors responsible for the pathogenesis of small cell lung carcinoma (SCLC). SCLC cells express cadherins, which are homophilic cell-cell adhesion molecules that play an important role in the regulation of metastasis. We present the first evidence that altering the activity of the small GTP-binding protein Rho induces cadherin-mediated adhesion. ADP-ribosylation of Rho upon incubation or electroporation with recombinant C3 exoenzyme induces rapid aggregation and compaction of SCLC cells. Aggregation and compaction induced by C3 exoenzyme are diminished by removal of extracellular Ca²⁺ and by the HECD blocking antibody to E-cadherin but not by antibodies to other adhesion molecules. Altering the activity of Rho by ADP-ribosylation does not alter surface expression of E-cadherin, but it alters G actin content, as indicated by the binding of DNase I. Treatment with cytochalasin D also alters G actin content and increases aggregation and compaction of SCLC cells. These findings implicate Rho in the regulation of cadherin-mediated adhesion and identify Rho as a potential therapeutic target for the control of SCLC metastasis.

¹ This research was supported by NIH Grant CA52471, Department of the Army Grant DAMD 17-94-J-4011, and Office of Naval Research Contract N0014-95-1-1278.

² To whom requests for reprints should be addressed. Phone: (717) 882-4650; Fax: (717) 882-5151; E-mail: cwilliam@inet.guthrie.org.

Received 11/27/96. Accepted 3/19/97.

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