Suppression of cell migration by protein kinase Cdelta

The ability of cancer cells to migrate is strongly correlated with malignant progression and metastasis. Survival signals that suppress apoptosis have also been linked to increased cell motility. We previously reported that suppression of protein kinase Cdelta (PKCdelta) provided survival signals in a rat fibroblast model system. These studies have been extended to human breast cancer cells with differential cell motilities and PKCdelta levels. BT-549 cells, which lack detectable expression of PKCdelta, migrate very efficiently, whereas MCF-7 cells, which express high levels of PKCdelta, migrate very poorly. Ectopic expression of PKCdelta suppressed cell migration in the BT-549 cells, and downregulation of PKCdelta enhanced cell migration in the MCF-7 cells. Downregulation of PKCdelta in the MCF-7 cells also led to increased secretion of the matrix metalloprotease MMP-9. The migration of mouse embryo fibroblasts (MEFs) from wild type and PKCdelta knockout mice was also examined and MEFs from PKCdelta knockout mice had a five-fold increase in cell migration relative to the wild-type MEFs. These data provide evidence that PKCdelta suppresses cell migration in both human breast cancer cells and in primary mouse fibroblasts, and indicate that the loss of PKCdelta in human cancers could contribute to both cell survival and metastasis.