The
E-cadherin/
catenin cell adhesion system is often down-regulatedin epithelial
tumors. This is thought to play an important role in
cancer invasion and
metastasis. Restoring this system may enable suppression of the metastatic spread of
cancer. This study examined the effect of
Src family kinase inhibitor PP2 on
E-cadherin-mediated cell-cell adhesion and metastatic potentials. In cell aggregation assays, PP2 stimulated the aggregation of colon, liver, and
breast cancer cells. In vitro cultures of
cancer cells showed that PP2 induced strong cell-cell contact. Immunoblot analysis showed that PP2 enhanced
E-cadherin/
catenin expression and that increased
E-cadherin/
catenin proteins were strongly associated with the actin cytoskeleton. Northern blot studies indicated that the observed increase of
E-cadherin/
catenin protein content was due to their increased gene expression. After the spleens of severe combined immunodeficient mice were inoculated with
cancer cells, treatment with PP2 for 3 weeks markedly reduced the rate of liver
metastasis, compared with the control counterparts. Our data demonstrate that PP2 can activate the functioning of the
E-cadherin-mediated cell adhesion system, which is associated with the suppression of
metastasis in
cancer cells. Thus, selective inhibition of Src activation may be potentially useful in the prevention of
cancer metastasis.